Allison W. Kurian, M.D., M.Sc.

All Publications

• Analysis of Breast Cancer Mortality in the US-1975 to 2019. JAMA Caswell-Jin, J. L., Sun, L. P., Munoz, D., Lu, Y., Li, Y., Huang, H., Hampton, J. M., Song, J., Jayasekera, J., Schechter, C., Alagoz, O., Stout, N. K., Trentham-Dietz, A., Lee, S. J., Huang, X., Mandelblatt, J. S., Berry, D. A., Kurian, A. W., Plevritis, S. K. 2024; 331 (3): 233-241

  Abstract

  Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated.Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer.Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence.The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years).According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

  View details for DOI 10.1001/jama.2023.25881

  View details for PubMedID 38227031

• Germline Genetic Testing After Cancer Diagnosis. JAMA Kurian, A. W., Abrahamse, P., Furgal, A., Ward, K. C., Hamilton, A. S., Hodan, R., Tocco, R., Liu, L., Berek, J. S., Hoang, L., Yussuf, A., Susswein, L., Esplin, E. D., Slavin, T. P., Gomez, S. L., Hofer, T. P., Katz, S. J. 2023

  Abstract

  Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention.To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019.Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia.The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing.Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type.Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

  View details for DOI 10.1001/jama.2023.9526

  View details for PubMedID 37276540

• Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer. Nature communications Ransohoff, J. D., Ritter, V., Purington, N., Andrade, K., Han, S., Liu, M., Liang, S. Y., John, E. M., Gomez, S. L., Telli, M. L., Schapira, L., Itakura, H., Sledge, G. W., Bhatt, A. S., Kurian, A. W. 2023; 14 (1): 2053

  Abstract

  Antimicrobial exposure during curative-intent treatment of triple-negative breast cancer (TNBC) may lead to gut microbiome dysbiosis, decreased circulating and tumor-infiltrating lymphocytes, and inferior outcomes. Here, we investigate the association of antimicrobial exposure and peripheral lymphocyte count during TNBC treatment with survival, using integrated electronic medical record and California Cancer Registry data in the Oncoshare database. Of 772 women with stage I-III TNBC treated with and without standard cytotoxic chemotherapy - prior to the immune checkpoint inhibitor era - most (654, 85%) used antimicrobials. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. This antimicrobial-mortality association is independent of changes in neutrophil count, is unrelated to disease severity, and is sustained through year three following diagnosis, suggesting antimicrobial exposure negatively impacts TNBC survival. These results may inform mechanistic studies and antimicrobial prescribing decisions in TNBC and other hormone receptor-independent cancers.

  View details for DOI 10.1038/s41467-023-37636-0

  View details for PubMedID 37045824

  View details for PubMedCentralID 5625777

• Breast Cancer Diagnosis, Treatment, and Outcomes of Patients From Sex and Gender Minority Groups. JAMA oncology Eckhert, E., Lansinger, O., Ritter, V., Liu, M., Han, S., Schapira, L., John, E. M., Gomez, S., Sledge, G., Kurian, A. W. 2023

  Abstract

  Sexual orientation and gender identity data are not collected by most hospitals or cancer registries; thus, little is known about the quality of breast cancer treatment for patients from sex and gender minority (SGM) groups.To evaluate the quality of breast cancer treatment and recurrence outcomes for patients from SGM groups compared with cisgender heterosexual patients.Exposure-matched retrospective case-control study of 92 patients from SGM groups treated at an academic medical center from January 1, 2008, to January 1, 2022, matched to cisgender heterosexual patients with breast cancer by year of diagnosis, age, tumor stage, estrogen receptor status, and ERBB2 (HER2) status.Patient demographic and clinical characteristics, as well as treatment quality, as measured by missed guideline-based breast cancer screening, appropriate referral for genetic counseling and testing, mastectomy vs lumpectomy, receipt of chest reconstruction, adjuvant radiation therapy after lumpectomy, neoadjuvant chemotherapy for stage III disease, antiestrogen therapy for at least 5 years for estrogen receptor-positive disease, ERBB2-directed therapy for ERBB2-positive disease, patient refusal of an oncologist-recommended treatment, time from symptom onset to tissue diagnosis, time from diagnosis to first treatment, and time from breast cancer diagnosis to first recurrence. Results were adjusted for multiple hypothesis testing. Compared with cisgender heterosexual patients, those from SGM groups were hypothesized to have disparities in 1 or more of these quality metrics.Ninety-two patients from SGM groups were matched to 92 cisgender heterosexual patients (n = 184). The median age at diagnosis for all patients was 49 years (IQR, 43-56 years); 74 were lesbian (80%), 12 were bisexual (13%), and 6 were transgender (6%). Compared with cisgender heterosexual patients, those from SGM groups experienced a delay in time from symptom onset to diagnosis (median time to diagnosis, 34 vs 64 days; multivariable adjusted hazard ratio, 0.65; 95% CI, 0.42-0.99; P = .04), were more likely to decline an oncologist-recommended treatment modality (35 [38%] vs 18 [20%]; multivariable adjusted odds ratio, 2.27; 95% CI, 1.09-4.74; P = .03), and were more likely to experience a breast cancer recurrence (multivariable adjusted hazard ratio, 3.07; 95% CI, 1.56-6.03; P = .001).This study found that among patients with breast cancer, those from SGM groups experienced delayed diagnosis, with faster recurrence at a 3-fold higher rate compared with cisgender heterosexual patients. These results suggest disparities in the care of patients from SGM groups and warrant further study to inform interventions.

  View details for DOI 10.1001/jamaoncol.2022.7146

  View details for PubMedID 36729432

• Reassessing the Benefits and Harms of Risk-Reducing Medication Considering the Persistent Risk of Breast Cancer Mortality in Estrogen Receptor-Positive Breast Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Jayasekera, J., Zhao, A., Schechter, C., Lowry, K., Yeh, J. M., Schwartz, M. D., O'Neill, S., Wernli, K. J., Stout, N., Mandelblatt, J., Kurian, A. W., Isaacs, C. 2022: JCO2201342

  Abstract

  Recent studies, including a meta-analysis of 88 trials, have shown higher than expected rates of recurrence and death in hormone receptor-positive breast cancer. These new findings suggest a need to re-evaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women.We adapted an established Cancer Intervention and Surveillance Modeling Network model to evaluate the lifetime benefits and harms of risk-reducing medication in women with a ≥ 3% 5-year risk of developing breast cancer according to the Breast Cancer Surveillance Consortium risk calculator. Model input parameters were derived from meta-analyses, clinical trials, and large observational data. We evaluated the effects of 5 years of risk-reducing medication (tamoxifen/aromatase inhibitors) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication. The modeled outcomes included invasive breast cancer, breast cancer death, side effects, false positives, and overdiagnosis. We conducted subgroup analyses for individual risk factors such as age, family history, and prior biopsy.Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no tamoxifen or screening. This is equivalent to an absolute reduction of 95 invasive breast cancers, and 42 breast cancer deaths per 1,000 high-risk women. However, these drugs are associated with side effects. For example, tamoxifen could increase the number of endometrial cancers up to 11 per 1,000 high-risk women. Benefits and harms varied by individual characteristics.The addition of risk-reducing medication to screening could further decrease the risk of breast cancer death. Clinical guidelines for high-risk women should consider integrating shared decision making for risk-reducing medication and screening on the basis of individual risk factors.

  View details for DOI 10.1200/JCO.22.01342

  View details for PubMedID 36455167

• Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis. JAMA oncology Lowry, K. P., Geuzinge, H. A., Stout, N. K., Alagoz, O., Hampton, J., Kerlikowske, K., de Koning, H. J., Miglioretti, D. L., van Ravesteyn, N. T., Schechter, C., Sprague, B. L., Tosteson, A. N., Trentham-Dietz, A., Weaver, D., Yaffe, M. J., Yeh, J. M., Couch, F. J., Hu, C., Kraft, P., Polley, E. C., Mandelblatt, J. S., Kurian, A. W., Robson, M. E. 2022

  Abstract

  Screening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these women.To estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants.This comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985.Screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years.Estimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges.The mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% [0.1%-0.2%] to 0.3% [0.2%-0.3%]) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women.This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.

  View details for DOI 10.1001/jamaoncol.2021.6204

  View details for PubMedID 35175286

• Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurian, A. W., Ward, K. C., Abrahamse, P. n., Bondarenko, I. n., Hamilton, A. S., Deapen, D. n., Morrow, M. n., Berek, J. S., Hofer, T. P., Katz, S. J. 2021: JCO2002785

  Abstract

  Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use.SEER records of women of age ≥ 20 years diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia were linked to the results of clinical germline testing through 2019. We measured testing trends, rates of variants of uncertain significance (VUS), and pathogenic variants (PVs).One quarter (25.2%) of 187,535 patients with breast cancer and one third (34.3%) of 14,689 patients with ovarian cancer were tested; annually, testing increased by 2%, whereas the number of genes tested increased by 28%. The prevalence of test results by gene category for breast cancer cases in 2017 were BRCA1/2, PVs 5.2%, and VUS 0.8%; breast cancer-associated genes or ovarian cancer-associated genes (ATM, BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53), PVs 3.7%, and VUS 12.0%; other actionable genes (APC, BMPR1A, MEN1, MUTYH, NF2, RB1, RET, SDHAF2, SDHB, SDHC, SDHD, SMAD4, TSC1, TSC2, and VHL) PVs 0.6%, and VUS 0.5%; and other genes, PVs 0.3%, and VUS 2.6%. For ovarian cancer cases in 2017, the prevalence of test results were BRCA1/2, PVs 11.0%, and VUS 0.9%; breast or ovarian genes, PVs 4.0%, and VUS 12.6%; other actionable genes, PVs 0.7%, and VUS 0.4%; and other genes, PVs 0.3%, and VUS 0.6%. VUS rates doubled over time (2013 diagnoses: 11.2%; 2017 diagnoses: 26.8%), particularly for racial or ethnic minorities (47.8% Asian and 46.0% Black, v 24.6% non-Hispanic White patients; P < .001).A testing gap persists for patients with ovarian cancer (34.3% tested v nearly all recommended), whereas adding more genes widened a racial or ethnic gap in VUS results. Most PVs were in 20 breast cancer-associated genes or ovarian cancer-associated genes; testing other genes yielded mostly VUS. Quality improvement should focus on testing indicated patients rather than adding more genes.

  View details for DOI 10.1200/JCO.20.02785

  View details for PubMedID 33560870

• Association of Genetic Testing Results with Mortality Among Women with Breast Cancer or Ovarian Cancer. Journal of the National Cancer Institute Kurian, A. W., Abrahamse, P., Bondarenko, I., Hamilton, A. S., Deapen, D., Gomez, S. L., Morrow, M., Berek, J. S., Hofer, T. P., Katz, S. J., Ward, K. C. 2021

  Abstract

  Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting.Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017; received chemotherapy; and linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality.22,495 breast and 4,320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35-0.69) and BRCA2 PVs (HR = 0.60, 95% CI = 0.41-0.89), and equivalent with PVs in other genes (HR = 0.65, 95% CI = 0.37-1.13), versus non-carriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR = 0.35, 95% CI = 0.25-0.49) and genes other than BRCA1/2 (HR = 0.47, 95% CI = 0.32-0.69). No PV was associated with higher cancer-specific mortality.Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than non-carriers. These results may reassure newly diagnosed patients and longer follow-up is ongoing.

  View details for DOI 10.1093/jnci/djab151

  View details for PubMedID 34373918

• Association of Germline Genetic Testing Results With Locoregional and Systemic Therapy in Patients With Breast Cancer. JAMA oncology Kurian, A. W., Ward, K. C., Abrahamse, P. n., Hamilton, A. S., Deapen, D. n., Morrow, M. n., Jagsi, R. n., Katz, S. J. 2020: e196400

  Abstract

  The increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer.To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer.For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017.Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions.Potential deviation of treatment from practice guidelines was assessed in the following clinical scenarios: (1) surgery: receipt of bilateral mastectomy by women eligible for less extensive unilateral surgery (unilateral breast tumor); (2) radiotherapy: omission in women indicated for postlumpectomy radiotherapy (all lumpectomy recipients except age ≥70 with stage I, estrogen and/or progesterone receptor [ER/PR] positive, ERBB2 [formerly HER2]-negative disease); and (3) chemotherapy: receipt by women eligible to consider chemotherapy omission (stages I-II, ER/PR-positive, ERBB2-negative, and 21-gene recurrence score of 0-30, which was the upper limit of the intermediate risk range during the study years). The adjusted percentage treated and adjusted odds ratio (OR) are reported based on multivariable modeling for each treatment-eligible group.A total of 20 568 women (17.3%) of 119 198 were eligible (mean [SD] age, 51.4 [12.2]). Compared with women whose test results were negative, those with BRCA1/2 pathogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76 (95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance.Women with pathogenic variants in BRCA1/2 and other breast cancer-associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.

  View details for DOI 10.1001/jamaoncol.2019.6400

  View details for PubMedID 32027353

• Prevalence of Pathogenic Variants in Cancer Susceptibility Genes Among Women With Postmenopausal Breast Cancer. JAMA Kurian, A. W., Bernhisel, R. n., Larson, K. n., Caswell-Jin, J. L., Shadyab, A. H., Ochs-Balcom, H. n., Stefanick, M. L. 2020; 323 (10): 995–97

  View details for DOI 10.1001/jama.2020.0229

  View details for PubMedID 32154851

• Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Ward, K. C., Howlader, N., Deapen, D., Hamilton, A. S., Mariotto, A., Miller, D., Penberthy, L. S., Katz, S. J. 2019; 37 (15): 1305-+

  View details for DOI 10.1200/JCO.18.01854

  View details for Web of Science ID 000468868300006

• Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Caswell-Jin, J. L., Zimmer, A. D., Stedden, W., Kingham, K. E., Zhou, A. Y., Kurian, A. W. 2019; 111 (1): 95–98

  View details for DOI 10.1093/jnci/djy147

  View details for Web of Science ID 000460623800016

• Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer JAMA ONCOLOGY Kurian, A. W., Ward, K. C., Hamilton, A. S., Deapen, D. M., Abrahamse, P., Bondarenko, I., Li, Y., Hawley, S. T., Morrow, M., Jagsi, R., Katz, S. J. 2018; 4 (8): 1066-1072

  View details for DOI 10.1001/jamaoncol.2018.0644

  View details for Web of Science ID 000441190200011

• Gaps in Receipt of Clinically Indicated Genetic Counseling After Diagnosis of Breast Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Katz, S. J., Ward, K. C., Hamilton, A. S., Mcleod, M. C., Wallner, L. P., Morrow, M. n., Jagsi, R. n., Hawley, S. T., Kurian, A. W. 2018: JCO2017762369

  Abstract

  Purpose Little is known about the extent to which genetic counseling is integrated into community practices for patients newly diagnosed with breast cancer. We examined the receipt of clinically indicated genetic counseling in these patients. Patients and Methods We surveyed 5,080 patients between the ages of 20 and 79 years, diagnosed from July 2013 to August 2015 with early-stage breast cancer and reported to the SEER registries of Georgia and Los Angeles County. Surveys were linked to SEER clinical data and genetic test results. The study sample (N = 1,711) comprised patients with indications for formal genetic risk evaluation. Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Three quarters (74.6%) received some form of genetic counseling (43.5%, formal counseling and 31.1%, physician-directed discussion). Virtually all tested patients (96.1%) reported some form of genetic discussion (62.2%, formal counseling and 33.9%, physician-directed discussion). However, only one half (50.6%) of those not tested received any discussion about genetics. Younger women were more likely to report some type of counseling, controlling for other factors: odds ratio, 4.5 (95% CI, 2.6 to 8.0); 1.9 (95% CI, 1.1 to 3.3); and 1.5 (95% CI, 1.0 to 2.3) for women younger than 50 years of age, 50 to 59 years of age, and 60 to 69 years of age versus those 70 years of age and older. Patients' assessments of the amount of information they received about whether to get tested were similarly high whether they were counseled by a genetics expert or by a physician only (80.8% v 79.4% stated information was just right, P = .59). Conclusion Less than one half (43.5%) of patients with clinical indications received formal genetic counseling. There is a large gap between mandates for timely pretest formal genetic counseling in higher-risk patients and the reality of practice today.

  View details for PubMedID 29528794

• Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer. Journal of clinical oncology Kurian, A. W., Li, Y., Hamilton, A. S., Ward, K. C., Hawley, S. T., Morrow, M., McLeod, M. C., Jagsi, R., Katz, S. J. 2017: JCO2016716480-?

  Abstract

  Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

  View details for DOI 10.1200/JCO.2016.71.6480

  View details for PubMedID 28402748

• Second Opinions From Medical Oncologists for Early-Stage Breast Cancer Prevalence, Correlates, and Consequences JAMA ONCOLOGY Kurian, A. W., Friese, C. R., Bondarenko, I., Jagsi, R., Li, Y., Hamilton, A. S., Ward, K. C., Katz, S. J. 2017; 3 (3): 391-397

  Abstract

  Advances in the evaluation and treatment of breast cancer have made the clinical decision-making context much more complex. A second opinion from a medical oncologist may facilitate decision making for women with breast cancer, yet little is known about second opinion use.To investigate the patterns and correlates of second opinion use and the effect on chemotherapy decisions.A total of 1901 women newly diagnosed with stages 0 to II breast cancer between July 2013 and September 2014 (response rate, 71.0%) were accrued through 2 population-based Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles County, California) and surveyed about their experiences with medical oncologists, decision making, and chemotherapy use.Factors associated with second opinion use were evaluated using logistic regression. Also assessed was the association between second opinion and chemotherapy use, adjusting for chemotherapy indication and propensity for receiving a second opinion. Multiple imputation and weighting were used to account for missing data.A total of 1901 patients with stage I to II breast cancer (mean [SD] age, 61.6 [11.0] years; 1071 [56.3%] non-Hispanic white) saw any medical oncologist. Analysis of multiply imputed, weighted data (mean n = 1866) showed that 168 (9.8%) (SE, 0.74%) received a second opinion and 54 (3.2%) (SE, 0.47%) received chemotherapy from the second oncologist. Satisfaction with chemotherapy decisions was high and did not differ between those who did (mean [SD], 4.3 [0.08] on a 1- to 5-point scale) or did not (4.4 [0.03]) obtain a second opinion (P = .29). Predictors of second opinion use included college education vs less education (odds ratio [OR], 1.85; 95% CI, 1.24-2.75), frequent use of internet-based support groups (OR, 2.15; 95% CI, 1.12-4.11), an intermediate result on the 21-gene recurrence score assay (OR, 1.85; 95% CI, 1.11-3.09), and a variant of uncertain significance on hereditary cancer genetic testing (OR, 3.24; 95% CI, 1.09-9.59). After controlling for patient and tumor characteristics, second opinion use was not associated with chemotherapy receipt (OR, 1.04; 95% CI, 0.71-1.52).Second opinion use was low (<10%) among patients with early-stage breast cancer, and high decision satisfaction regardless of second opinion use suggests little unmet demand. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. Patient demand for second opinions may increase as more complex genomic tests are disseminated.

  View details for DOI 10.1001/jamaoncol.2016.5652

  View details for Web of Science ID 000397491400018

• Genetic Testing and Counseling Among Patients With Newly Diagnosed Breast Cancer . JAMA Kurian, A. W., Griffith, K. A., Hamilton, A. S., Ward, K. C., Morrow, M. n., Katz, S. J., Jagsi, R. n. 2017; 317 (5): 531–34

  View details for PubMedID 28170472

• Recent Trends in Chemotherapy Use and Oncologists' Treatment Recommendations for Early-Stage Breast Cancer. Journal of the National Cancer Institute Kurian, A. W., Bondarenko, I. n., Jagsi, R. n., Friese, C. R., McLeod, M. C., Hawley, S. T., Hamilton, A. S., Ward, K. C., Hofer, T. P., Katz, S. J. 2017

  Abstract

  There is growing concern about overtreatment of breast cancer as outcomes have improved over time. However, little is known about how chemotherapy use and oncologists' recommendations have changed in recent years.We surveyed 5080 women (70% response rate) diagnosed with breast cancer between 2013 and 2015 and accrued through two Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles) about chemotherapy receipt and their oncologists' chemotherapy recommendations. We surveyed 504 attending oncologists (60.3% response rate ) about chemotherapy recommendations in node-negative and node-positive case scenarios. We conducted descriptive statistics of chemotherapy use and patients' report of oncologists' recommendations and used a generalized linear mixed model of chemotherapy use according to time and clinical factors. All statistical tests were two-sided.The analytic sample was 2926 patients with stage I-II, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. From 2013 to 2015, keeping other factors constant, chemotherapy use was estimated to decline from 34.5% (95% confidence interval [CI] = 30.8% to 38.3%) to 21.3% (95% CI = 19.0% to 23.7%, P < .001). Estimated decline in chemotherapy use was from 26.6% (95% CI = 23.0% to 30.7%) to 14.1% (95% CI = 12.0% to 16.3%) for node-negative/micrometastasis patients and from 81.1% (95% CI = 76.6% to 85.0%) to 64.2% (95% CI = 58.6% to 69.6%) for node-positive patients. Use of the 21-gene recurrence score (RS) did not change among node-negative/micrometastasis patients, and increasing RS use in node-positive patients accounted for one-third of the chemotherapy decline. Patients' report of oncologists' recommendations for chemotherapy declined from 44.9% (95% CI = 40.2% to 49.7%) to 31.6% (95% CI = 25.9% to 37.9%), controlling for other factors. Oncologists were much more likely to order RS if patient preferences were discordant with their recommendations (67.4%, 95% CI = 61.7% to 73.0%, vs 17.5%, 95% CI = 13.1% to 22.0%, concordant), and they adjusted recommendations based on patient preferences and RS results.For both node-negative/micrometastasis and node-positive patients, chemotherapy receipt and oncologists' recommendations for chemotherapy declined markedly over time, without substantial change in practice guidelines. Results of ongoing trials will be essential to confirm the quality of this approach to breast cancer care.

  View details for PubMedID 29237009

• Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA-the journal of the American Medical Association Kurian, A. W., Lichtensztajn, D. Y., Keegan, T. H., Nelson, D. O., Clarke, C. A., Gomez, S. L. 2014; 312 (9): 902-914

  Abstract

  Bilateral mastectomy is increasingly used to treat unilateral breast cancer. Because it may have medical and psychosocial complications, a better understanding of its use and outcomes is essential to optimizing cancer care.To compare use of and mortality after bilateral mastectomy, breast-conserving therapy with radiation, and unilateral mastectomy.Observational cohort study within the population-based California Cancer Registry; participants were women diagnosed with stages 0-III unilateral breast cancer in California from 1998 through 2011, with median follow-up of 89.1 months.Factors associated with surgery use (from polytomous logistic regression); overall and breast cancer-specific mortality (from propensity score weighting and Cox proportional hazards analysis).Among 189,734 patients, the rate of bilateral mastectomy increased from 2.0% (95% CI, 1.7%-2.2%) in 1998 to 12.3% (95% CI, 11.8%-12.9%) in 2011, an annual increase of 14.3% (95% CI, 13.1%-15.5%); among women younger than 40 years, the rate increased from 3.6% (95% CI, 2.3%-5.0%) in 1998 to 33% (95% CI, 29.8%-36.5%) in 2011. Bilateral mastectomy was more often used by non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute (NCI)-designated cancer center (8.6% [95% CI, 8.1%-9.2%] among NCI cancer center patients vs 6.0% [95% CI, 5.9%-6.1%] among non-NCI cancer center patients; odds ratio [OR], 1.13 [95% CI, 1.04-1.22]); in contrast, unilateral mastectomy was more often used by racial/ethnic minorities (Filipina, 52.8% [95% CI, 51.6%-54.0%]; OR, 2.00 [95% CI, 1.90-2.11] and Hispanic, 45.6% [95% CI, 45.0%-46.2%]; OR, 1.16 [95% CI, 1.13-1.20] vs non-Hispanic white, 35.2% [95% CI, 34.9%-35.5%]) and those with public/Medicaid insurance (48.4% [95% CI, 47.8%-48.9%]; OR, 1.08 [95% CI, 1.05-1.11] vs private insurance, 36.6% [95% CI, 36.3%-36.8%]). Compared with breast-conserving surgery with radiation (10-year mortality, 16.8% [95% CI, 16.6%-17.1%]), unilateral mastectomy was associated with higher all-cause mortality (hazard ratio [HR], 1.35 [95% CI, 1.32-1.39]; 10-year mortality, 20.1% [95% CI, 19.9%-20.4%]). There was no significant mortality difference compared with bilateral mastectomy (HR, 1.02 [95% CI, 0.94-1.11]; 10-year mortality, 18.8% [95% CI, 18.6%-19.0%]). Propensity analysis showed similar results.Use of bilateral mastectomy increased significantly throughout California from 1998 through 2011 and was not associated with lower mortality than that achieved with breast-conserving surgery plus radiation. Unilateral mastectomy was associated with higher mortality than were the other 2 surgical options.

  View details for DOI 10.1001/jama.2014.10707

  View details for PubMedID 25182099

• Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Hare, E. E., Mills, M. A., Kingham, K. E., McPherson, L., Whittemore, A. S., McGuire, V., Ladabaum, U., Kobayashi, Y., Lincoln, S. E., Cargill, M., Ford, J. M. 2014; 32 (19): 2001-2009

  Abstract

  Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample.Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at -80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants.In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants of uncertain significance among 42 genes.Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.

  View details for DOI 10.1200/JCO.2013.53.6607

  View details for Web of Science ID 000337925500007

• Online Tool to Guide Decisions for BRCA1/2 Mutation Carriers JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Munoz, D. F., Rust, P., Schackmann, E. A., Smith, M., Clarke, L., Mills, M. A., Plevritis, S. K. 2012; 30 (5): 497-506

  Abstract

  Women with BRCA1 or BRCA2 (BRCA1/2) mutations must choose between prophylactic surgeries and screening to manage their high risks of breast and ovarian cancer, comparing options in terms of cancer incidence, survival, and quality of life. A clinical decision tool could guide these complex choices.We built a Monte Carlo model for BRCA1/2 mutation carriers, simulating breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years and prophylactic mastectomy (PM) and/or prophylactic oophorectomy (PO) at various ages. Modeled outcomes were cancer incidence, tumor features that shape treatment recommendations, overall survival, and cause-specific mortality. We adapted the model into an online tool to support shared decision making.We compared strategies on cancer incidence and survival to age 70 years; for example, PO plus PM at age 25 years optimizes both outcomes (incidence, 4% to 11%; survival, 80% to 83%), whereas PO at age 40 years plus MRI screening offers less effective prevention, yet similar survival (incidence, 36% to 57%; survival, 74% to 80%). To characterize patients' treatment and survivorship experiences, we reported the tumor features and treatments associated with risk-reducing interventions; for example, in most BRCA2 mutation carriers (81%), MRI screening diagnoses stage I, hormone receptor-positive breast cancers, which may not require chemotherapy.Cancer risk-reducing options for BRCA1/2 mutation carriers vary in their impact on cancer incidence, recommended treatments, quality of life, and survival. To guide decisions informed by multiple health outcomes, we provide an online tool for joint use by patients with their physicians (http://brcatool.stanford.edu).

  View details for DOI 10.1200/JCO.2011.38.6060

  View details for PubMedID 22231042

• Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Gong, G. D., John, E. M., Johnston, D. A., Felberg, A., West, D. W., Miron, A., Andrulis, I. L., Hopper, J. L., Knight, J. A., Ozcelik, H., Dite, G. S., Apicella, C., Southey, M. C., Whittemore, A. S. 2011; 29 (34): 4505-4509

  Abstract

  Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs).Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors.We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases.These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.

  View details for DOI 10.1200/JCO.2010.34.4440

  View details for PubMedID 22042950

  View details for PubMedCentralID PMC3236651

• Survival Analysis of Cancer Risk Reduction Strategies for BRCA1/2 Mutation Carriers JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Sigal, B. M., Plevritis, S. K. 2010; 28 (2): 222-231

  Abstract

  Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death.We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers.With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%).Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

  View details for DOI 10.1200/JCO.2009.22.7991

  View details for PubMedID 19996031

• Second Primary Breast Cancer Occurrence According to Hormone Receptor Status JOURNAL OF THE NATIONAL CANCER INSTITUTE Kurian, A. W., McClure, L. A., John, E. M., Horn-Ross, P. L., Ford, J. M., Clarke, C. A. 2009; 101 (15): 1058-1065

  Abstract

  Contralateral second primary breast cancers occur in 4% of female breast cancer survivors. Little is known about differences in risk for second primary breast cancers related to the estrogen and progesterone receptor (hormone receptor [HR]) status of the first tumor.We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral primary breast cancers among 4927 women diagnosed with a first breast cancer between January 1, 1992, and December 31, 2004, using the National Cancer Institute's Surveillance, Epidemiology, and End Results database.For women whose first breast tumors were HR positive, risk of contralateral primary breast cancer was elevated, compared with the general population, adjusted for age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk [AR] = 13 cases per 10 000 person-years [PY]), and was not related to the HR status of the second tumor. For women whose first breast tumors were HR negative, the risk of a contralateral primary tumor was statistically significantly higher than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI = 3.38 to 3.78, AR = 18 per 10 000 PY), and it was associated with a much greater likelihood of an HR-negative second tumor (SIR for HR-positive second tumors = 1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10 000 PY; SIR for HR-negative second tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10 000 PY). Women who were initially diagnosed with HR-negative tumors when younger than 30 years had greatly elevated risk of HR-negative contralateral tumors, compared with the general population (SIR = 169, 95% CI = 106 to 256, AR = 77 per 10 000 PY). Incidence rates for any contralateral primary cancer following an HR-negative or HR-positive tumor were higher in non-Hispanic blacks, Hispanics, and Asians or Pacific Islanders than in non-Hispanic whites.Risk for contralateral second primary breast cancers varies substantially by HR status of the first tumor, age, and race and/or ethnicity. Women with HR-negative first tumors have nearly a 10-fold elevated risk of developing HR-negative second tumors, compared with the general population. These findings warrant intensive surveillance for second breast cancers in women with HR-negative tumors.

  View details for DOI 10.1093/jnci/djp181

  View details for Web of Science ID 000268812900007

  View details for PubMedID 19590058

  View details for PubMedCentralID PMC2720990

• Performance of BRCA1/2 mutation prediction models in Asian Americans JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Gong, G. D., Chun, N. M., Mills, M. A., Staton, A. D., Kingham, K. E., Crawford, B. B., Lee, R., Chan, S., Donlon, S. S., Ridge, Y., Panabaker, K., West, D. W., Whittemore, A. S., Ford, J. M. 2008; 26 (29): 4752-8

  View details for DOI 10.1200/JCO.2008.16.8310

• A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Newton Thompson, R., Gaw, A. F., Arai, S., Ortiz, R., Garber, A. M. 2007; 25 (6): 634-641

  Abstract

  One-year adjuvant trastuzumab (AT) therapy, with or without anthracyclines, increases disease-free and overall survival in early-stage HER2/neu-positive breast cancer. We sought to evaluate the cost effectiveness of these regimens, which are expensive and potentially toxic.We used a Markov health-state transition model to simulate three adjuvant therapy options for a cohort of 49-year-old women with HER2/neu-positive early-stage breast cancer: conventional chemotherapy without trastuzumab; anthracycline-based AT regimens used in the National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831 trials; and the nonanthracycline AT regimen used in the Breast Cancer International Research group 006 trial. The base case used treatment efficacy measures reported in the randomized clinical trials of AT. We measured health outcomes in quality-adjusted life-years (QALYs) and costs in 2005 United States dollars (US dollars) and subjected results to probabilistic sensitivity analysis.In the base case, the anthracycline-based AT arm has an incremental cost-effectiveness ratio (ICER) of 39,982 dollars/QALY, whereas the nonanthracycline AT arm is more expensive and less effective; this result is insensitive to changes in recurrence rates, but if there is no benefit after 4 years, ICERs exceed 100,000 dollars/QALY for both AT arms. Results are moderately sensitive to variation in breast cancer survival rates and trastuzumab cost, and less sensitive to variations in cardiac toxicity.AT has an ICER comparable to those for other widely used interventions. Longer clinical follow-up is warranted to evaluate the long-term efficacy and toxicity of different AT regimens.

  View details for DOI 10.1200/JCO.2006.06.3081

  View details for Web of Science ID 000244384000006

  View details for PubMedID 17308268

• A scoping review of web-based, interactive, personalized decision-making tools available to support breast cancer treatment and survivorship care. Journal of cancer survivorship : research and practice Wojcik, K. M., Kamil, D., Zhang, J., Wilson, O. W., Smith, L., Butera, G., Isaacs, C., Kurian, A., Jayasekera, J. 2024

  Abstract

  We reviewed existing personalized, web-based, interactive decision-making tools available to guide breast cancer treatment and survivorship care decisions in clinical settings.The study was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We searched PubMed and related databases for interactive web-based decision-making tools developed to support breast cancer treatment and survivorship care from 2013 to 2023. Information on each tool's purpose, target population, data sources, individual and contextual characteristics, outcomes, validation, and usability testing were extracted. We completed a quality assessment for each tool using the International Patient Decision Aid Standard (IPDAS) instrument.We found 54 tools providing personalized breast cancer outcomes (e.g., recurrence) and treatment recommendations (e.g., chemotherapy) based on individual clinical (e.g., stage), genomic (e.g., 21-gene-recurrence score), behavioral (e.g., smoking), and contextual (e.g., insurance) characteristics. Forty-five tools were validated, and nine had undergone usability testing. However, validation and usability testing included mostly White, educated, and/or insured individuals. The average quality assessment score of the tools was 16 (range: 6-46; potential maximum: 63).There was wide variation in the characteristics, quality, validity, and usability of the tools. Future studies should consider diverse populations for tool development and testing.There are tools available to support personalized breast cancer treatment and survivorship care decisions in clinical settings. It is important for both cancer survivors and physicians to carefully consider the quality, validity, and usability of these tools before using them to guide care decisions.

  View details for DOI 10.1007/s11764-024-01567-6

  View details for PubMedID 38538922

  View details for PubMedCentralID 5682364

• Tumor-Infiltrating lymphocytes and breast cancer mortality in racially and ethnically diverse participants of the Northern California breast cancer family registry. JNCI cancer spectrum Ransohoff, J. D., Miller, I., Koo, J., Joshi, V., Kurian, A. W., Allison, K. H., John, E. M., Telli, M. L. 2024

  Abstract

  Stromal tumor-infiltrating lymphocyte (sTIL) enrichment in pre-treatment breast tumors has been associated with superior response to neoadjuvant treatment and survival. In a population-based cohort, we studied sTIL-survival associations by race and ethnicity. We assessed associations of continuous sTIL scores and sTIL-enriched breast cancers (defined as percent lymphocytic infiltration of tumor stroma or cell nests at cutoffs of 30%, 50%, and 70%) with clinical and epidemiologic characteristics and conducted multivariable survival analyses. While we identified no difference in sTIL score by race and ethnicity, higher continuous sTIL score was associated with lower breast cancer-specific mortality only among non-Hispanic White and Asian American but not African American and Hispanic women. This finding suggests that complex factors influence treatment response and survival, given that sTIL enrichment was not associated with a survival advantage among women from minoritized groups, who more often experience health disparities. Further study of patient selection for sTIL-guided treatment strategies is warranted.

  View details for DOI 10.1093/jncics/pkae023

  View details for PubMedID 38547391

• Incidence of Nonkeratinocyte Skin Cancer After Breast Cancer Radiation Therapy. JAMA network open Rezaei, S. J., Eid, E., Tang, J. Y., Kurian, A. W., Kwong, B. Y., Linos, E. 2024; 7 (3): e241632

  Abstract

  Previous studies have suggested that radiation therapy may contribute to an increased risk of subsequent nonkeratinocyte (ie, not squamous and basal cell) skin cancers.To test the hypothesis that radiation therapy for breast cancer increases the risk of subsequent nonkeratinocyte skin cancers, particularly when these cancers are localized to the skin of the breast or trunk.This population-based cohort study used longitudinal data from the Surveillance, Epidemiology, and End Results (SEER) Program for January 1, 2000, to December 31, 2019. The SEER database includes population-based cohort data from 17 registries. Patients with newly diagnosed breast cancer were identified and were evaluated for subsequent nonkeratinocyte skin cancer development. Data analysis was performed from January to August 2023.Radiation therapy, chemotherapy, or surgery for breast cancer.The primary outcomes were standardized incidence ratios (SIRs) for subsequent nonkeratinocyte skin cancer development from 2000 to 2019 based on treatment type (radiation therapy, chemotherapy, or surgery), skin cancer site on the body, and skin cancer subtype.Among the 875 880 patients with newly diagnosed breast cancer included in this study, 99.3% were women, 51.6% were aged older than 60 years, and 50.3% received radiation therapy. A total of 11.2% patients identified as Hispanic, 10.1% identified as non-Hispanic Black, and 69.5% identified as non-Hispanic White. From 2000 to 2019, there were 3839 patients with nonkeratinocyte skin cancer, including melanoma (3419 [89.1%]), Merkel cell carcinoma (121 [3.2%]), hemangiosarcoma (104 [2.7%]), and 32 other nonkeratinocyte skin cancers (195 [5.1%]), documented to occur after breast cancer treatment. The risk of nonkeratinocyte skin cancer diagnosis after breast cancer treatment with radiation was 57% higher (SIR, 1.57 [95% CI, 1.45-1.7]) than that of the general population when considering the most relevant site: the skin of the breast or trunk. When risk at this site was stratified by skin cancer subtype, the SIRs for melanoma and hemangiosarcoma were both statistically significant at 1.37 (95% CI, 1.25-1.49) and 27.11 (95% CI, 21.6-33.61), respectively. Receipt of radiation therapy was associated with a greater risk of nonkeratinocyte skin cancer compared with chemotherapy and surgical interventions.In this study of patients with breast cancer, an increased risk of melanoma and hemangiosarcoma after breast cancer treatment with radiation therapy was observed. Although occurrences of nonkeratinocyte skin cancers are rare, physicians should be aware of this elevated risk to help inform follow-up care.

  View details for DOI 10.1001/jamanetworkopen.2024.1632

  View details for PubMedID 38457179

• Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology Guideline Q and A. JCO oncology practice Kurian, A. W., Bedrosian, I., Kohlmann, W. K., Somerfield, M. R., Robson, M. E. 2024: OP2300771

  View details for DOI 10.1200/OP.23.00771

  View details for PubMedID 38252903

• Avoiding lead-time bias by estimating stage-specific proportions of cancer and non-cancer deaths. Cancer causes & control : CCC Chang, E. T., Clarke, C. A., Colditz, G. A., Kurian, A. W., Hubbell, E. 2024

  Abstract

  Understanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening.Using data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50-84 years at cancer diagnosis in 2006-2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020.Most cancer patients diagnosed at stages I-II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I-II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I-II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach.Across all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I-II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened.

  View details for DOI 10.1007/s10552-023-01842-4

  View details for PubMedID 38238615

  View details for PubMedCentralID 2677921

• Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Bedrosian, I., Somerfield, M. R., Achatz, M. I., Boughey, J. C., Curigliano, G., Friedman, S., Kohlmann, W. K., Kurian, A. W., Laronga, C., Lynce, F., Norquist, B. S., Plichta, J. K., Rodriguez, P., Shah, P. D., Tischkowitz, M., Wood, M., Yadav, S., Yao, K., Robson, M. E. 2024: JCO2302225

  Abstract

  To develop recommendations for germline mutation testing for patients with breast cancer.An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process.Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations.BRCA1/2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/2 testing, regardless of family history. BRCA1/2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

  View details for DOI 10.1200/JCO.23.02225

  View details for PubMedID 38175972

• Management of the Gene-Positive Patient Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2023: 1249

  View details for Web of Science ID 001126452500014

• Personalizing Treatment for Early-Stage Breast Cancer Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2023: 1249

  View details for Web of Science ID 001126452500017

• NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024. Journal of the National Comprehensive Cancer Network : JNCCN Daly, M. B., Pal, T., Maxwell, K. N., Churpek, J., Kohlmann, W., AlHilli, Z., Arun, B., Buys, S. S., Cheng, H., Domchek, S. M., Friedman, S., Giri, V., Goggins, M., Hagemann, A., Hendrix, A., Hutton, M. L., Karlan, B. Y., Kassem, N., Khan, S., Khoury, K., Kurian, A. W., Laronga, C., Mak, J. S., Mansour, J., McDonnell, K., Menendez, C. S., Merajver, S. D., Norquist, B. S., Offit, K., Rash, D., Reiser, G., Senter-Jamieson, L., Shannon, K. M., Visvanathan, K., Welborn, J., Wick, M. J., Wood, M., Yurgelun, M. B., Dwyer, M. A., Darlow, S. D. 2023; 21 (10): 1000-1010

  Abstract

  The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

  View details for DOI 10.6004/jnccn.2023.0051

  View details for PubMedID 37856201

• Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives. Journal of the National Cancer Institute Heald, B., Pirzadeh-Miller, S., Ellsworth, R. E., Nielsen, S. M., Russell, E. M., Beitsch, P., Esplin, E. D., Nussbaum, R. L., Pineda-Alvarez, D. E., Kurian, A. W., Hampel, H. 2023

  Abstract

  Current guidelines recommend single gene/variant testing in relatives of patients with known pathogenic or likely pathogenic variants (PGVs) in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have PGVs in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3,696 relatives of 7,433 probands. Unexpected PGVs were identified in 230 (6.2%) relatives, including 144 who were negative for the familial PGV but positive for a PGV in a different gene than the proband and 74 who tested positive for the familial PGV and had an additional PGV in a different gene than the proband. Of the relatives with unexpected PGVs, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial PGV would have resulted in missed, actionable findings for a subset of relatives.

  View details for DOI 10.1093/jnci/djad203

  View details for PubMedID 37756683

• Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer. JAMA network open Su, C. C., Wu, J. T., Choi, E., Myall, N. J., Neal, J. W., Kurian, A. W., Stehr, H., Wood, D., Henry, S. M., Backhus, L. M., Leung, A. N., Wakelee, H. A., Han, S. S. 2023; 6 (9): e2335813

  Abstract

  Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).To evaluate the association of metastatic disease type on overall survival (OS) among patients with non-small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.Cohort study of a national US population based at a tertiary referral center in the San Francisco Bay Area using participant data from the National Lung Screening Trial (NLST) who were enrolled between 2002 and 2004 and followed up for up to 7 years as the primary cohort and patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 and followed up for up to 13 years as the validation cohort. Participants from NLST with de novo metastatic or distant recurrent NSCLC diagnoses were included. Data were analyzed from January 2021 to March 2023.De novo stage IV vs distant recurrent metastatic disease.OS after diagnosis of metastatic disease.The NLST and SHC cohort consisted of 660 and 180 participants, respectively (411 men [62.3%] vs 109 men [60.6%], 602 White participants [91.2%] vs 111 White participants [61.7%], and mean [SD] age of 66.8 [5.5] vs 71.4 [7.9] years at metastasis, respectively). Patients with distant recurrence showed significantly better OS than patients with de novo metastasis (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.60-0.87; P < .001) in NLST, which was replicated in SHC (aHR, 0.64; 95% CI, 0.43-0.96; P = .03). In SHC, patients with de novo metastasis more frequently progressed to the bone (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 patients with de novo metastasis [33.3%] vs 8 patients with distant recurrence [13.3%]) than patients with distant recurrence and were primarily detected through symptoms (102 patients [85.0%]) as compared with posttreatment surveillance (47 patients [78.3%]) in the latter. The main finding remained consistent after further adjusting for metastasis sites and detection methods.In this cohort study, patients with distant recurrent NSCLC had significantly better OS than those with de novo disease, and the latter group was associated with characteristics that may affect overall survival. This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.

  View details for DOI 10.1001/jamanetworkopen.2023.35813

  View details for PubMedID 37751203

• Recurrent BRCA2 exon 3 deletion in Assyrian families. Journal of medical genetics Hodan, R., Kingham, K., Kurian, A. W. 2023

  Abstract

  We identified six patients from five families with a recurrent mutation: NM_000059.3 (BRCA2) exon 3 deletion. All families self-identified as Assyrian. Assyrians are an ethnoreligious population of ancient Mesopotamia, now mostly living in modern day Iraq, Syria, Turkey and Iran. They are historically a socially isolated population with intermarriage within their community, living as a religious and language minority in mostly Muslim countries. The probands of each family presented with a classic BRCA2-associated cancer including early-onset breast cancer, epithelial serous ovarian cancer, male breast cancer and/or high-grade prostate cancer, and family history that was also significant for BRCA2-associated cancer. BRCA2 exon 3 deletion is classified as pathogenic and has been previously described in the literature, but it has not been described as a founder mutation in a particular population. We characterise this recurrent BRCA2 pathogenic variant in five Assyrian families in a single centre cohort.

  View details for DOI 10.1136/jmg-2023-109430

  View details for PubMedID 37657917

• Endometrial Cancer Risk Among Germline BRCA1/2 Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps. JCO precision oncology Sorouri, K., Lynce, F., Feltmate, C. M., Davis, M. R., Muto, M. G., Konstantinopoulos, P. A., Stover, E. H., Kurian, A. W., Hill, S. J., Partridge, A. H., Tolaney, S. M., Garber, J. E., Bychkovsky, B. L. 2023; 7: e2300290

  Abstract

  To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline BRCA1/2 pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population.A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among BRCA1/2 PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined.Patients with BRCA1/2 PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to BRCA1/2 PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of BRCA1/2 PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions.This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with BRCA1/2 PVs. Evidence-based clinical guidelines for rr-hysterectomy in BRCA1/2 PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either BRCA1 or BRCA2 PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in BRCA1/2 PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for BRCA1/2 PV carriers.

  View details for DOI 10.1200/PO.23.00290

  View details for PubMedID 38061009

• A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry. Breast cancer research : BCR Middha, P., Wang, X., Behrens, S., Bolla, M. K., Wang, Q., Dennis, J., Michailidou, K., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Auer, P. L., Augustinsson, A., Baert, T., Freeman, L. E., Becher, H., Beckmann, M. W., Benitez, J., Bojesen, S. E., Brauch, H., Brenner, H., Brooks-Wilson, A., Campa, D., Canzian, F., Carracedo, A., Castelao, J. E., Chanock, S. J., Chenevix-Trench, G., Cordina-Duverger, E., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Dossus, L., Dugué, P. A., Eliassen, A. H., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J. D., Fletcher, O., Flyger, H., Gabrielson, M., Gago-Dominguez, M., Giles, G. G., González-Neira, A., Grassmann, F., Grundy, A., Guénel, P., Haiman, C. A., Håkansson, N., Hall, P., Hamann, U., Hankinson, S. E., Harkness, E. F., Holleczek, B., Hoppe, R., Hopper, J. L., Houlston, R. S., Howell, A., Hunter, D. J., Ingvar, C., Isaksson, K., Jernström, H., John, E. M., Jones, M. E., Kaaks, R., Keeman, R., Kitahara, C. M., Ko, Y. D., Koutros, S., Kurian, A. W., Lacey, J. V., Lambrechts, D., Larson, N. L., Larsson, S., Le Marchand, L., Lejbkowicz, F., Li, S., Linet, M., Lissowska, J., Martinez, M. E., Maurer, T., Mulligan, A. M., Mulot, C., Murphy, R. A., Newman, W. G., Nielsen, S. F., Nordestgaard, B. G., Norman, A., O'Brien, K. M., Olson, J. E., Patel, A. V., Prentice, R., Rees-Punia, E., Rennert, G., Rhenius, V., Ruddy, K. J., Sandler, D. P., Scott, C. G., Shah, M., Shu, X. O., Smeets, A., Southey, M. C., Stone, J., Tamimi, R. M., Taylor, J. A., Teras, L. R., Tomczyk, K., Troester, M. A., Truong, T., Vachon, C. M., Wang, S. S., Weinberg, C. R., Wildiers, H., Willett, W., Winham, S. J., Wolk, A., Yang, X. R., Zamora, M. P., Zheng, W., Ziogas, A., Dunning, A. M., Pharoah, P. D., García-Closas, M., Schmidt, M. K., Kraft, P., Milne, R. L., Lindström, S., Easton, D. F., Chang-Claude, J. 2023; 25 (1): 93

  Abstract

  Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94).Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.

  View details for DOI 10.1186/s13058-023-01691-8

  View details for PubMedID 37559094

  View details for PubMedCentralID 3488186

• Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel. Journal of medical genetics Levi, H., Carmi, S., Rosset, S., Yerushalmi, R., Zick, A., Yablonski-Peretz, T., Wang, Q., Bolla, M. K., Dennis, J., Michailidou, K., Lush, M., Ahearn, T., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Arndt, V., Augustinsson, A., Auvinen, P., Beane Freeman, L., Beckmann, M., Behrens, S., Bermisheva, M., Bodelon, C., Bogdanova, N. V., Bojesen, S. E., Brenner, H., Byers, H., Camp, N., Castelao, J., Chang-Claude, J., Chirlaque, M. D., Chung, W., Clarke, C., Collee, M. J., Colonna, S., Couch, F., Cox, A., Cross, S. S., Czene, K., Daly, M., Devilee, P., Dork, T., Dossus, L., Eccles, D. M., Eliassen, A. H., Eriksson, M., Evans, G., Fasching, P., Fletcher, O., Flyger, H., Fritschi, L., Gabrielson, M., Gago-Dominguez, M., García-Closas, M., Garcia-Saenz, J. A., Genkinger, J., Giles, G. G., Goldberg, M., Guénel, P., Hall, P., Hamann, U., He, W., Hillemanns, P., Hollestelle, A., Hoppe, R., Hopper, J., Jakovchevska, S., Jakubowska, A., Jernström, H., John, E., Johnson, N., Jones, M., Vijai, J., Kaaks, R., Khusnutdinova, E., Kitahara, C., Koutros, S., Kristensen, V., Kurian, A. W., Lacey, J., Lambrechts, D., Le Marchand, L., Lejbkowicz, F., Lindblom, A., Loibl, S., Lori, A., Lubinski, J., Mannermaa, A., Manoochehri, M., Mavroudis, D., Menon, U., Mulligan, A., Murphy, R., Nevelsteen, I., Newman, W. G., Obi, N., O'Brien, K., Offit, K., Olshan, A., Plaseska-Karanfilska, D., Olson, J., Panico, S., Park-Simon, T. W., Patel, A., Peterlongo, P., Rack, B., Radice, P., Rennert, G., Rhenius, V., Romero, A., Saloustros, E., Sandler, D., Schmidt, M. K., Schwentner, L., Shah, M., Sharma, P., Simard, J., Southey, M., Stone, J., Tapper, W. J., Taylor, J., Teras, L., Toland, A. E., Troester, M., Truong, T., van der Kolk, L. E., Weinberg, C., Wendt, C., Yang, X. R., Zheng, W., Ziogas, A., Dunning, A. M., Pharoah, P., Easton, D. F., Ben-Sachar, S., Elefant, N., Shamir, R., Elkon, R. 2023

  Abstract

  Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.

  View details for DOI 10.1136/jmg-2023-109185

  View details for PubMedID 37451831

• Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer medicine Morra, A., Schreurs, M. A., Andrulis, I. L., Anton-Culver, H., Augustinsson, A., Beckmann, M. W., Behrens, S., Bojesen, S. E., Bolla, M. K., Brauch, H., Broeks, A., Buys, S. S., Camp, N. J., Castelao, J. E., Cessna, M. H., Chang-Claude, J., Chung, W. K., Colonna, S. V., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Dennis, J., Devilee, P., Dörk, T., Dunning, A. M., Dwek, M., Easton, D. F., Eccles, D. M., Eriksson, M., Evans, D. G., Fasching, P. A., Fehm, T. N., Figueroa, J. D., Flyger, H., Gabrielson, M., Gago-Dominguez, M., García-Closas, M., García-Sáenz, J. A., Genkinger, J., Grassmann, F., Gündert, M., Hahnen, E., Haiman, C. A., Hamann, U., Harrington, P. A., Hartikainen, J. M., Hoppe, R., Hopper, J. L., Houlston, R. S., Howell, A., Jakubowska, A., Janni, W., Jernström, H., John, E. M., Johnson, N., Jones, M. E., Kristensen, V. N., Kurian, A. W., Lambrechts, D., Le Marchand, L., Lindblom, A., Lubiński, J., Lux, M. P., Mannermaa, A., Mavroudis, D., Mulligan, A. M., Muranen, T. A., Nevanlinna, H., Nevelsteen, I., Neven, P., Newman, W. G., Obi, N., Offit, K., Olshan, A. F., Park-Simon, T. W., Patel, A. V., Peterlongo, P., Phillips, K. A., Plaseska-Karanfilska, D., Polley, E. C., Presneau, N., Pylkäs, K., Rack, B., Radice, P., Rashid, M. U., Rhenius, V., Robson, M., Romero, A., Saloustros, E., Sawyer, E. J., Schmutzler, R. K., Schuetze, S., Scott, C., Shah, M., Smichkoska, S., Southey, M. C., Tapper, W. J., Teras, L. R., Tollenaar, R. A., Tomczyk, K., Tomlinson, I., Troester, M. A., Vachon, C. M., van Veen, E. M., Wang, Q., Wendt, C., Wildiers, H., Winqvist, R., Ziogas, A., Hall, P., Pharoah, P. D., Adank, M. A., Hollestelle, A., Schmidt, M. K., Hooning, M. J. 2023

  Abstract

  Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death.There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

  View details for DOI 10.1002/cam4.6272

  View details for PubMedID 37401034

• Elevated cancer risk among individuals with combinations of cancer-related risk factors: A large claims database analysis. Cong, Z., Ye, X., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002690

• Genetic testing into survivorship after diagnosis of breast cancer. Katz, S., Hodan, R., Abrahamse, P., Tocco, R., Hofer, T., Wallner, L. P., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002710

• Polygenic risk score calibration and association with breast cancer in diverse ancestries Kucera, M., Hughes, E., Mabey, B., Hullinger, B., Pederson, H., Pal, T., Domchek, S. M., Eng, C., Garber, J., Gordon, O., Klemp, J. R., Mukherjee, S., Vijai, J., Pruthi, S., Kurian, A. W., Whitworth, P. W., Lanchbury, J., Slavin, T., Gutin, A., Olopade, O. I. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002635

• Germline genetic testing use and results after a cancer diagnosis Kurian, A. W., Abrahamse, P., Furgal, A., Ward, K. C., Hamilton, A. S., Hodan, R., Liu, L., Berek, J. S., Hoang, L., Yussuf, A., Susswein, L. R., Esplin, E. D., Slavin, T., Gomez, S. L., Hofer, T., Katz, S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002630

• Examining the potential for lead-time bias by estimating stage-specific proportions of deaths due to diagnosed cancer. Chang, E. T., Clarke, C. A., Colditz, G. A., Gomez, S. L., Kurian, A. W., Hubbell, E. A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002665

• Real-world clinical outcomes in patients (pts) with HR+/HER2-metastatic breast cancer (mBC) treated with chemotherapy (CT) in the United States (US) Tolaney, S. M., Punie, K., Kurian, A. W., Ntalla, I., Verret, W., Sadetsky, N., Sjekloca, N., Stokes, M., Jhaveri, K. L. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772004430

• Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations. BJOG : an international journal of obstetrics and gynaecology Nebgen, D. R., Domchek, S. M., Kotsopoulos, J., de Hullu, J. A., Crosbie, E. J., Paramanandam, V. S., van Zanten, M. B., Norquist, B. M., Guise, T., Rozenberg, S., Kurian, A. W., Pederson, H. J., Yuksel, N., Michaelson-Cohen, R., Bober, S. L., da Silva Filho, A. L., Johansen, N., Guidozzi, F., Evans, D. G., Menon, U., Kingsberg, S. A., Powell, C. B., Grandi, G., Marchetti, C., Jacobson, M., Brennan, D. J., Hickey, M. 2023

  Abstract

  Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

  View details for DOI 10.1111/1471-0528.17511

  View details for PubMedID 37132126

• Emotion regulation and choice of bilateral mastectomy for the treatment of unilateral breast cancer. Cancer medicine Zhang, J. X., Kurian, A. W., Jo, B., Nouriani, B., Neri, E., Gross, J. J., Spiegel, D. 2023

  Abstract

  There has been steadily increasing use of bilateral mastectomy (BMX) in the treatment of primary breast cancer (BC). In this study, we utilized functional magnetic resonance imaging (fMRI) to examine the influence of emotion regulation on the decision of newly diagnosed BC patients to choose BMX rather than non-BMX treatments.We recruited 123 women with unilateral BC, 61 of whom received BMX and 62 of whom received non-BMX treatments, and 39 healthy controls. While participants were in the fMRI scanner, we showed them BC-related and non-BC-negative images. In one condition, they were instructed to watch the images naturally. In another, they were instructed to regulate their negative emotion. We compared the fMRI signal during these conditions throughout the brain.With non-BC-negative images as the baseline, BC patients showed greater self-reported reactivity and neural reactivity to BC-related images in brain regions associated with self-reflection than did controls. Among the BC patients, the BMX group showed weaker activation in prefrontal emotion regulation brain regions during emotion regulation than did the non-BMX group.BC patients are understandably emotionally hyper-reactive to BC-related stimuli and those who ultimately received BMX experience more difficulty in regulating BC-related negative emotion than non-BMX BC patients. These findings offer neuropsychological evidence that difficulty in managing anxiety related to the possibility of cancer recurrence is a factor in surgical treatment decision-making and may be an intervention target with the goal of strengthening the management of cancer-related anxiety by nonsurgical means.NCT03050463.

  View details for DOI 10.1002/cam4.5963

  View details for PubMedID 37083300

• The association between age at breast cancer diagnosis and prevalence of pathogenic variants. Breast cancer research and treatment Daly, M. B., Rosenthal, E., Cummings, S., Bernhisel, R., Kidd, J., Hughes, E., Gutin, A., Meek, S., Slavin, T. P., Kurian, A. W. 2023

  Abstract

  Young age at breast cancer (BC) diagnosis and family history of BC are strongly associated with high prevalence of pathogenic variants (PVs) in BRCA1 and BRCA2 genes. There is limited evidence for such associations with moderate/high penetrance BC-risk genes such as ATM, CHEK2, and PALB2.We analyzed multi-gene panel testing results (09/2013-12/2019) for women unaffected by any cancer (N = 371,594) and those affected with BC (N = 130,151) ascertained for suspicion of hereditary breast and/or ovarian cancer. Multivariable logistic regression was used to test association between PV status and age at BC diagnosis (≤ 45 vs. > 45 years) or family history of BC after controlling for personal/family non-BC histories and self-reported ancestry.An association between young age (≤ 45 years) at diagnosis and presence of PVs was strong for BRCA1 (OR 3.95, 95% CI 3.64-4.29) and moderate for BRCA2 (OR 1.98, 95% CI 1.84-2.14). Modest associations were observed between PVs and young age at diagnosis for ATM (OR 1.22, 95% CI 1.08-1.37) and CHEK2 (OR 1.34, 95% CI 1.21-1.47) genes, but not for PALB2 (OR 1.12, 95% CI 0.98-1.27). For women with BC, earliest age of familial BC diagnosis followed a similar pattern. For unaffected women, earliest age of family cancer diagnosis was significantly associated with PV status only for BRCA1 (OR 2.34, 95% CI 2.13-2.56) and BRCA2 (OR 1.25, 95% CI 1.16-1.35).Young age at BC diagnosis is not a strong risk factor for carrying PVs in BC-associated genes ATM, CHEK2, or PALB2.

  View details for DOI 10.1007/s10549-023-06946-8

  View details for PubMedID 37084156

  View details for PubMedCentralID 7469614

• Clinical implications of conflicting variant interpretations in the cancer genetics clinic. Genetics in medicine : official journal of the American College of Medical Genetics Zukin, E., Culver, J. O., Liu, Y., Yang, Y., Ricker, C. N., Hodan, R., Sturgeon, D., Kingham, K., Chun, N. M., Rowe-Teeter, C., Singh, K., Zell, J. A., Ladabaum, U., McDonnell, K. J., Ford, J. M., Parmigiani, G., Braun, D., Kurian, A. W., Gruber, S. B., Idos, G. E. 2023: 100837

  Abstract

  To describe the clinical impact of commercial laboratories issuing conflicting classifications of genetic variants.Results from 2,000 patients undergoing a multi-gene hereditary cancer panel by a single laboratory were analyzed. Clinically significant discrepancies between the lab provided test reports and other major commercial laboratories were identified, including differences between pathogenic/likely pathogenic (P/LP) and variant of uncertain significance (VUS) classifications, via review of ClinVar archives. For patients carrying a VUS, clinical documentation was assessed for evidence of provider awareness of the conflict.50/975 (5.1%) patients with non-negative results carried a variant with a clinically significant conflict, 19 with a P/LP variant reported in APC or MUTYH, and 31 with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. Only 10/28 (36%) patients with a VUS with a clinically significant conflict had a documented discussion by a provider about the conflict. Discrepant counseling strategies were utilized for different patients with the same variant. Among patients with a CDKN2A variant or a monoallelic MUTYH variant, providers were significantly more likely to make recommendations based on the laboratory-reported classification.Our findings highlight the frequency of variant interpretation discrepancies and importance of clinician awareness. Guidance is needed on managing patients with discrepant variants to support accurate risk assessment.

  View details for DOI 10.1016/j.gim.2023.100837

  View details for PubMedID 37057674

• POSTER SESSION D: PILOT STUDY OF 'ROADMAP TO PARENTHOOD' DECISION AID AND PLANNING TOOL FOR FAMILY BUILDING AFTER CANCER Benedict, C., Simon, P., Spiegel, D., Kurian, A. W., Alvero, R., Berek, J. S., Philip, E. J., Schapira, L. OXFORD UNIV PRESS INC. 2023: S533

  View details for Web of Science ID 001042977901464

• Disparity in Breast Cancer Care: Current State of Access to Screening, Genetic Testing, Oncofertility, and Reconstruction. Journal of the American College of Surgeons Crown, A., Fazeli, S., Kurian, A. W., Ochoa, D. A., Joseph, K. A. 2023

  Abstract

  Breast cancer is the most common cancer diagnosed in women, accounting for an estimated 30% of all new women cancer diagnoses in 2022. Advances in breast cancer treatment have reduced the mortality rates over the past 25 years by up to 34% but not all groups have benefitted equally from these improvements. These disparities span the continuum of care from screening to the receipt of guideline-concordant therapy and survivorship. At the 2022 American College of Surgeons Clinical Congress, a panel session was dedicated to educating and discussing methods of addressing these disparities in a coordinated manner. While there are multilevel solutions to address these disparities, this paper focuses on screening, genetic testing, reconstruction, and oncofertility.

  View details for DOI 10.1097/XCS.0000000000000647

  View details for PubMedID 36971366

• Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions. Journal of the National Cancer Institute Lindström, S., Wang, L., Feng, H., Majumdar, A., Huo, S., Macdonald, J., Harrison, T., Turman, C., Chen, H., Mancuso, N., Bammler, T., Gallinger, S., Gruber, S. B., Gunter, M. J., Le Marchand, L., Moreno, V., Offit, K., de Vivo, I., O'Mara, T. A., Spurdle, A. B., Tomlinson, I., Fitzgerald, R., Gharahkhani, P., Gockel, I., Jankowski, J., Macgregor, S., Schumacher, J., Barnholtz-Sloan, J., Bondy, M. L., Houlston, R. S., Jenkins, R. B., Melin, B., Wrensch, M., Brennan, P., Christiani, D., Johansson, M., Mckay, J., Aldrich, M. C., Amos, C. I., Landi, M. T., Tardon, A., Bishop, D. T., Demenais, F., Goldstein, A. M., Iles, M. M., Kanetsky, P. A., Law, M. H., Amundadottir, L. T., Stolzenberg-Solomon, R., Wolpin, B. M., Klein, A., Petersen, G., Risch, H., Chanock, S. J., Purdue, M. P., Scelo, G., Pharoah, P., Kar, S., Hung, R. J., Pasaniuc, B., Kraft, P. 2023

  Abstract

  The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from twelve cancer genome-wide association studies (GWAS) to quantify pair-wise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.We collected GWAS summary statistics for twelve solid cancers based on 376,759 cancer cases and 532,864 controls of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies (TWAS) to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.We observed wide-spread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and TWAS, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least two cancer types by testing for pleiotropy at known cancer susceptibility loci.Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer- and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.

  View details for DOI 10.1093/jnci/djad043

  View details for PubMedID 36929942

• Cascade Genetic Risk Education and Testing in Families With Hereditary Cancer Syndromes: A Pilot Study. JCO oncology practice Katz, S. J., Abrahamse, P., Hodan, R., Kurian, A. W., Rankin, A., Tocco, R. S., Rios-Ventura, S., Ward, K. C., An, L. C. 2023: OP2200677

  Abstract

  Cascade genetic risk evaluation in families with hereditary cancer can reduce the burden of disease but the rate of germline genetic testing in relatives of patients at risk is low.We identified all 277 women diagnosed with breast cancer in Georgia in 2017 who linked to a clinically actionable germline pathogenic variant through a Surveillance, Epidemiology, and End Results registry-variant linkage initiative. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. We randomly assigned patient-family clusters at the time of the patient enrollment offer to free versus $50 (USD) test cost. Patients invited relatives to join the study through personalized e-mail. Enrolled relatives received online cancer genetic education and the opportunity to order clinical germline genetic testing through the platform. The primary outcome was the number of relatives who ordered genetic testing.One hundred twenty-five of 277 patients completed surveys (45.2%). Most respondents were eligible for the trial offer (113 of 125; 90.4%). In the free testing arm, 20 of 56 eligible patients participated (35.7% of eligible respondents) and they invited 28 relatives: 12 relatives enrolled and 10 ordered testing. In the $50 (USD) arm, 16 of 57 eligible patients participated (28.1%) and they invited 38 relatives: 18 relatives enrolled and 17 ordered testing.Cascade genetic testing in families with hereditary cancer syndromes accrued through a population-based cancer registry can be achieved through an online platform that offers genetic risk education and low-cost testing to relatives. A modest charge did not appear to influence the percentage of participating patients, numbers of participating relatives, and numbers of relatives who received genetic testing.

  View details for DOI 10.1200/OP.22.00677

  View details for PubMedID 36921235

• Changes in breast cancer risk and risk factor profiles among U.S.-born and immigrant Asian American women residing in the San Francisco Bay Area. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology John, E. M., Koo, J., Ingles, S. A., Kurian, A. W., Hines, L. M. 2023

  Abstract

  Breast cancer incidence rates in women of Asian descent have been increasing in the United States (U.S.) and Asia.In a case-control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort.Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951-1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women (OR=1.40, 95% CI=0.97-2.03) and two-fold among foreign-born Chinese women (OR=2.16, 95% CI=1.21-3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics.In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women.It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs.

  View details for DOI 10.1158/1055-9965.EPI-22-1128

  View details for PubMedID 36780232

• Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry. Genome medicine Mueller, S. H., Lai, A. G., Valkovskaya, M., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Lush, M., Abu-Ful, Z., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Augustinsson, A., Baert, T., Freeman, L. E., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Blomqvist, C., Bogdanova, N. V., Bojesen, S. E., Bonanni, B., Brenner, H., Brucker, S. Y., Buys, S. S., Castelao, J. E., Chan, T. L., Chang-Claude, J., Chanock, S. J., Choi, J. Y., Chung, W. K., Colonna, S. V., Cornelissen, S., Couch, F. J., Czene, K., Daly, M. B., Devilee, P., Dörk, T., Dossus, L., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Engel, C., Evans, D. G., Fasching, P. A., Fletcher, O., Flyger, H., Gago-Dominguez, M., Gao, Y. T., García-Closas, M., García-Sáenz, J. A., Genkinger, J., Gentry-Maharaj, A., Grassmann, F., Guénel, P., Gündert, M., Haeberle, L., Hahnen, E., Haiman, C. A., Håkansson, N., Hall, P., Harkness, E. F., Harrington, P. A., Hartikainen, J. M., Hartman, M., Hein, A., Ho, W. K., Hooning, M. J., Hoppe, R., Hopper, J. L., Houlston, R. S., Howell, A., Hunter, D. J., Huo, D., Ito, H., Iwasaki, M., Jakubowska, A., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Kang, D., Khusnutdinova, E. K., Kim, S. W., Kitahara, C. M., Koutros, S., Kraft, P., Kristensen, V. N., Kubelka-Sabit, K., Kurian, A. W., Kwong, A., Lacey, J. V., Lambrechts, D., Le Marchand, L., Li, J., Linet, M., Lo, W. Y., Long, J., Lophatananon, A., Mannermaa, A., Manoochehri, M., Margolin, S., Matsuo, K., Mavroudis, D., Menon, U., Muir, K., Murphy, R. A., Nevanlinna, H., Newman, W. G., Niederacher, D., O'Brien, K. M., Obi, N., Offit, K., Olopade, O. I., Olshan, A. F., Olsson, H., Park, S. K., Patel, A. V., Patel, A., Perou, C. M., Peto, J., Pharoah, P. D., Plaseska-Karanfilska, D., Presneau, N., Rack, B., Radice, P., Ramachandran, D., Rashid, M. U., Rennert, G., Romero, A., Ruddy, K. J., Ruebner, M., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schmidt, M. K., Schmutzler, R. K., Schneider, M. O., Scott, C., Shah, M., Sharma, P., Shen, C. Y., Shu, X. O., Simard, J., Surowy, H., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Teo, S. H., Teras, L. R., Toland, A. E., Tollenaar, R. A., Torres, D., Torres-Mejía, G., Troester, M. A., Truong, T., Vachon, C. M., Vijai, J., Weinberg, C. R., Wendt, C., Winqvist, R., Wolk, A., Wu, A. H., Yamaji, T., Yang, X. R., Yu, J. C., Zheng, W., Ziogas, A., Ziv, E., Dunning, A. M., Easton, D. F., Hemingway, H., Hamann, U., Kuchenbaecker, K. B. 2023; 15 (1): 7

  Abstract

  Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts.

  View details for DOI 10.1186/s13073-022-01152-5

  View details for PubMedID 36703164

• Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Lopes Cardozo, J. M., Andrulis, I. L., Bojesen, S. E., Dörk, T., Eccles, D. M., Fasching, P. A., Hooning, M. J., Keeman, R., Nevanlinna, H., Rutgers, E. J., Easton, D. F., Hall, P., Pharoah, P. D., van 't Veer, L. J., Schmidt, M. K. 2023: JCO2201978

  Abstract

  A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.The PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.An increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

  View details for DOI 10.1200/JCO.22.01978

  View details for PubMedID 36689693

• Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Yadav, S., Boddicker, N. J., Na, J., Polley, E. C., Hu, C., Hart, S. N., Gnanaolivu, R. D., Larson, N., Holtegaard, S., Huang, H., Dunn, C. A., Teras, L. R., Patel, A. V., Lacey, J. V., Neuhausen, S. L., Martinez, E., Haiman, C., Chen, F., Ruddy, K. J., Olson, J. E., John, E. M., Kurian, A. W., Sandler, D. P., O'Brien, K. M., Taylor, J. A., Weinberg, C. R., Anton-Culver, H., Ziogas, A., Zirpoli, G., Goldgar, D. E., Palmer, J. R., Domchek, S. M., Weitzel, J. N., Nathanson, K. L., Kraft, P., Couch, F. J. 2023: JCO2201239

  Abstract

  To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2.The study population included 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for PV carriers in each gene compared with women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status.Germline BRCA1, BRCA2, and CHEK2 PV carriers with breast cancer were at significantly elevated risk (hazard ratio > 1.9) of CBC, whereas only the PALB2 PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). By contrast, ATM PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 PV carriers with breast cancer and 35% for PALB2 PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2.Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.

  View details for DOI 10.1200/JCO.22.01239

  View details for PubMedID 36623243

• A hybrid modelling approach for abstracting CT imaging indications by integrating natural language processing from radiology reports with structured data from electronic health records. Khan, A., Wu, J., Choi, E., Graber-Naidich, A., Henry, S., Wakelee, H. A., Kurian, A. W., Liang, S., Leung, A., Langlotz, C., Backhus, L. M., Han, S. S. AMER ASSOC CANCER RESEARCH. 2023

  View details for Web of Science ID 001057852300077

• Perspectives of private payers on multicancer early-detection tests: informing research, implementation, and policy Health Affairs Scholar Trosman, J. R., Weldon, C. B., Kurian, A. W., Pasquinelli, M. M., Kircher, S. M., Martin, N., Douglas, M. P., Phillips, K. A. 2023; 1 (1): qxad005

  View details for DOI 10.1093/haschl/qxad005

• Risk factors for second primary lung cancer among breast cancer survivors Choi, E., Lee, J., Wu, J. T., Wakelee, H. A., Schapira, L., Kurian, A. W., Han, S. S. AMER ASSOC CANCER RESEARCH. 2023

  View details for Web of Science ID 001057852300067

• Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics. American journal of human genetics Jia, G., Ping, J., Shu, X., Yang, Y., Cai, Q., Kweon, S. S., Choi, J. Y., Kubo, M., Park, S. K., Bolla, M. K., Dennis, J., Wang, Q., Guo, X., Li, B., Tao, R., Aronson, K. J., Chan, T. L., Gao, Y. T., Hartman, M., Ho, W. K., Ito, H., Iwasaki, M., Iwata, H., John, E. M., Kasuga, Y., Kim, M. K., Kurian, A. W., Kwong, A., Li, J., Lophatananon, A., Low, S. K., Mariapun, S., Matsuda, K., Matsuo, K., Muir, K., Noh, D. Y., Park, B., Park, M. H., Shen, C. Y., Shin, M. H., Spinelli, J. J., Takahashi, A., Tseng, C., Tsugane, S., Wu, A. H., Yamaji, T., Zheng, Y., Dunning, A. M., Pharoah, P. D., Teo, S. H., Kang, D., Easton, D. F., Simard, J., Shu, X. O., Long, J., Zheng, W. 2022

  Abstract

  By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p < 5.0 × 10-8 and a Bonferroni-corrected p < 4.6 × 10-6, respectively. Of them, 32 loci and 15 genes showed a significantly different association between ER-positive and ER-negative breast cancer after Bonferroni correction. Significant ancestral differences in risk variant allele frequencies and their association strengths with breast cancer risk were identified. Of the significant associations identified in this study, 17 loci and 14 genes are located 1Mb away from any of the previously reported breast cancer risk variants. Pathways analyses including 221 putative risk genes identified multiple signaling pathways that may play a significant role in the development of breast cancer. Our study provides a comprehensive understanding of and new biological insights into the genetics of this common malignancy.

  View details for DOI 10.1016/j.ajhg.2022.10.011

  View details for PubMedID 36356581

• Reducing the risk of breast cancer. Cleveland Clinic journal of medicine Pederson, H. J., Al-Hilli, Z., Kurian, A. W. 2022; 89 (11): 643-652

  Abstract

  Breast cancer remains the most common female malignancy in the United States. Reducing this cancer burden involves identification of high-risk individuals and personalized risk management. Because coronary artery disease remains the primary cause of death for women, any intervention to reduce breast cancer risk must be weighed against comorbidities and interventions affecting cardiovascular risk reduction. For select women at increased risk for breast cancer, preventive medication can greatly decrease risk and is vastly underutilized. Women's health clinicians are poised to evaluate risk, promote breast cancer risk reduction, and manage overall health.

  View details for DOI 10.3949/ccjm.89a.21113

  View details for PubMedID 36319046

• Development and Validation of a Breast Cancer Polygenic Risk Score on the Basis of Genetic Ancestry Composition. JCO precision oncology Hughes, E., Wagner, S., Pruss, D., Bernhisel, R., Probst, B., Abkevich, V., Simmons, T., Hullinger, B., Judkins, T., Rosenthal, E., Roa, B., Domchek, S. M., Eng, C., Garber, J., Gary, M., Klemp, J., Mukherjee, S., Offit, K., Olopade, O. I., Vijai, J., Weitzel, J. N., Whitworth, P., Yehia, L., Gordon, O., Pederson, H., Kurian, A., Slavin, T. P., Gutin, A., Lanchbury, J. S. 2022; 6: e2200084

  Abstract

  Polygenic risk scores (PRSs) for breast cancer (BC) risk stratification have been developed primarily in women of European ancestry. Their application to women of non-European ancestry has lagged because of the lack of a formal approach to incorporate genetic ancestry and ancestry-dependent variant frequencies and effect sizes. Here, we propose a multiple-ancestry PRS (MA-PRS) that addresses these issues and may be useful in the development of equitable PRSs across other cancers and common diseases.Women referred for hereditary cancer testing were divided into consecutive cohorts for development (n = 189,230) and for independent validation (n = 89,126). Individual genetic composition as fractions of three reference ancestries (African, East Asian, and European) was determined from ancestry-informative single-nucleotide polymorphisms. The MA-PRS is a combination of three ancestry-specific PRSs on the basis of genetic ancestral composition. Stratification of risk was evaluated by multivariable logistic regression models controlling for family cancer history. Goodness-of-fit analysis compared expected with observed relative risks by quantiles of the MA-PRS distribution.In independent validation, the MA-PRS was significantly associated with BC risk in the full cohort (odds ratio, 1.43; 95% CI, 1.40 to 1.46; P = 8.6 × 10-308) and within each major ancestry. The top decile of the MA-PRS consistently identified patients with two-fold increased risk of developing BC. Goodness-of-fit tests showed that the MA-PRS was well calibrated and predicted BC risk accurately in the tails of the distribution for both European and non-European women.The MA-PRS uses genetic ancestral composition to expand the utility of polygenic risk prediction to non-European women. Inclusion of genetic ancestry in polygenic risk prediction presents an opportunity for more personalized treatment decisions for women of varying and mixed ancestries.

  View details for DOI 10.1200/PO.22.00084

  View details for PubMedID 36331239

• Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study. British journal of sports medicine Dixon-Suen, S. C., Lewis, S. J., Martin, R. M., English, D. R., Boyle, T., Giles, G. G., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Lush, M., Investigators, A., Ahearn, T. U., Ambrosone, C. B., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Augustinsson, A., Auvinen, P., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Bermisheva, M., Blomqvist, C., Bogdanova, N. V., Bojesen, S. E., Bonanni, B., Brenner, H., Brüning, T., Buys, S. S., Camp, N. J., Campa, D., Canzian, F., Castelao, J. E., Cessna, M. H., Chang-Claude, J., Chanock, S. J., Clarke, C. L., Conroy, D. M., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dörk, T., Dwek, M., Eccles, D. M., Eliassen, A. H., Engel, C., Eriksson, M., Evans, D. G., Fasching, P. A., Fletcher, O., Flyger, H., Fritschi, L., Gabrielson, M., Gago-Dominguez, M., García-Closas, M., García-Sáenz, J. A., Goldberg, M. S., Guénel, P., Gündert, M., Hahnen, E., Haiman, C. A., Häberle, L., Håkansson, N., Hall, P., Hamann, U., Hart, S. N., Harvie, M., Hillemanns, P., Hollestelle, A., Hooning, M. J., Hoppe, R., Hopper, J., Howell, A., Hunter, D. J., Jakubowska, A., Janni, W., John, E. M., Jung, A., Kaaks, R., Keeman, R., Kitahara, C. M., Koutros, S., Kraft, P., Kristensen, V. N., Kubelka-Sabit, K., Kurian, A. W., Lacey, J. V., Lambrechts, D., Le Marchand, L., Lindblom, A., Loibl, S., Lubiński, J., Mannermaa, A., Manoochehri, M., Margolin, S., Martinez, M. E., Mavroudis, D., Menon, U., Mulligan, A. M., Murphy, R. A., Collaborators, N., Nevanlinna, H., Nevelsteen, I., Newman, W. G., Offit, K., Olshan, A. F., Olsson, H., Orr, N., Patel, A., Peto, J., Plaseska-Karanfilska, D., Presneau, N., Rack, B., Radice, P., Rees-Punia, E., Rennert, G., Rennert, H. S., Romero, A., Saloustros, E., Sandler, D. P., Schmidt, M. K., Schmutzler, R. K., Schwentner, L., Scott, C., Shah, M., Shu, X. O., Simard, J., Southey, M. C., Stone, J., Surowy, H., Swerdlow, A. J., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Terry, M. B., Tollenaar, R. A., Troester, M. A., Truong, T., Untch, M., Vachon, C. M., Joseph, V., Wappenschmidt, B., Weinberg, C. R., Wolk, A., Yannoukakos, D., Zheng, W., Ziogas, A., Dunning, A. M., Pharoah, P. D., Easton, D. F., Milne, R. L., Lynch, B. M. 2022; 56 (20): 1157-1170

  Abstract

  Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

  View details for DOI 10.1136/bjsports-2021-105132

  View details for PubMedID 36328784

• A pilot study to increase cascade genetic risk education and testing in families with hereditary cancer syndromes. Katz, S., Hawley, S. T., Tocco, R., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2022: 378

  View details for Web of Science ID 000891944700374

• Change in practice of RRSO consults and procedures during the COVID-19 pandemic O'Mara, A., Kurian, A., Benedict, C., Diver, E. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2022: S275

  View details for Web of Science ID 000892333600112

• Constitutional BRCA1 Methylation and Risk of Incident Triple-Negative Breast Cancer and High-grade Serous Ovarian Cancer. JAMA oncology Lønning, P. E., Nikolaienko, O., Pan, K., Kurian, A. W., Eikesdal, H. P., Pettinger, M., Anderson, G. L., Prentice, R. L., Chlebowski, R. T., Knappskog, S. 2022

  Abstract

  About 25% of all triple-negative breast cancers (TNBCs) and 10% to 20% of high-grade serous ovarian cancers (HGSOCs) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC or HGSOC is unknown.To assess the potential association between white blood cell BRCA1 promoter methylation and subsequent risk of incident TNBC and HGSOC.This case-control study included women who were participating in the Women's Health Initiative study who had not received a diagnosis of either breast or ovarian cancer before study entrance. A total of 637 women developing incident TNBC and 511 women developing incident HGSOC were matched with cancer-free controls (1841 and 2982, respectively) in a nested case-control design. Cancers were confirmed after central medical record review. Blood samples, which were collected at entry, were analyzed for BRCA1 promoter methylation by massive parallel sequencing. The study was performed in the Mohn Cancer Research Laboratory (Bergen, Norway) between 2019 and 2022.Associations between BRCA1 methylation and incident TNBC and incident HGSOC were analyzed by Cox proportional hazards regression.Of 2478 cases and controls in the TNBC group and 3493 cases and controls in the HGSOC group, respectively, 7 (0.3%) and 3 (0.1%) were American Indian or Alaska Native, 46 (1.9%) and 30 (0.9%) were Asian, 1 (0.04%) and 1 (0.03%) was Native Hawaiian or Pacific Islander, 326 (13.2%) and 125 (3.6%) were Black or African, 56 (2.3%) and 116 (3.3%) were Hispanic, 2046 (82.6%) and 3257 (93.2%) were White, and 35 (1.4%) and 35 (1.0%) were multiracial. Median (range) age at entry was 62 (50-79) years, with a median interval to diagnosis of 9 (TNBC) and 10 (HGSOC) years. Methylated BRCA1 alleles were present in 194 controls (5.5%). Methylation was associated with risk of incident TNBC (12.4% methylated; HR, 2.35; 95% CI, 1.70-3.23; P < .001) and incident HGSOC (9.4% methylated; HR, 1.93; 95% CI, 1.36-2.73; P < .001). Restricting analyses to individuals with more than 5 years between sampling and cancer diagnosis yielded similar results (TNBC: HR, 2.52; 95% CI, 1.75-3.63; P < .001; HGSOC: HR, 1.82; 95% CI, 1.22-2.72; P = .003). Across individuals, methylation was not haplotype-specific, arguing against an underlying cis-acting factor. Within individuals, BRCA1 methylation was observed on the same allele, indicating clonal expansion from a single methylation event. There was no association found between BRCA1 methylation and germline pathogenic variant status.The results of this case-control suggest that constitutional normal tissue BRCA1 promoter methylation is significantly associated with risk of incident TNBC and HGSOC, with potential implications for prediction of these cancers. These findings warrant further research to determine if constitutional methylation of tumor suppressor genes are pancancer risk factors.

  View details for DOI 10.1001/jamaoncol.2022.3846

  View details for PubMedID 36074460

• Incident comorbidities after tamoxifen or aromatase inhibitor therapy in a racially and ethnically diverse cohort of women with breast cancer. Breast cancer research and treatment Gupta, T., Purington, N., Liu, M., Han, S., Sledge, G., Schapira, L., Kurian, A. W. 2022

  Abstract

  As survival with early-stage, hormone receptor (HR)-positive breast has improved, it is essential to understand the long-term risks of incident comorbidities with different adjuvant endocrine therapy (ET) options.Women treated with tamoxifen and/or an aromatase inhibitor (AI) for stages 1-3, HR-positive/HER2-negative breast cancer from 2000 to 2016 in either of two healthcare systems in the San Francisco Bay Area were included. We considered the following comorbidities: cerebrovascular accidents, congestive heart failure, dementia, depression/anxiety, diabetes mellitus, hyperlipidemia, myocardial infarction, non-alcoholic steatohepatitis, osteoporosis/fracture, peripheral vascular disease, and venous thromboembolism. Cause-specific Cox proportional hazards models were fit to time-to-new-diagnosis for each comorbidity, accounting for death as a competing risk. Hazard ratios (HR) and 95% confidence intervals (CI) for tamoxifen versus AI were reported.Among 2,902 analyzed patients, the median age at diagnosis was 58.3 years; 67.6% were non-Hispanic white, 22.3% Asian, 7.5% Hispanic, and 1.7% non-Hispanic Black. Half (54.7%) used AIs only, 27.6% used tamoxifen only and 17.7% used both tamoxifen and AIs sequentially. Tamoxifen was associated with a lower risk of osteoporosis than AI (multivariable HR 0.45, 95% CI 0.32-0.62). No other incident comorbidity risk varied between users of tamoxifen versus AIs.In a diverse, multi-institutional, contemporary breast cancer cohort, the only incident comorbidity that differed between ET options was osteoporosis, a known side effect of AIs. These results may inform clinical decision-making about ET, and reassure patients who have bothersome symptoms on AIs that they are unlikely to develop worse comorbidities if they switch to tamoxifen.

  View details for DOI 10.1007/s10549-022-06716-y

  View details for PubMedID 36030472

• The effect of COVID-19 on telehealth: next steps in a post-pandemic life. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics Liang, S. Y., Richardson, M. T., Wong, D., Chen, T., Colocci, N., Kapp, D. S., de Bruin, M., Kurian, A., Chan, J. K. 2022

  View details for DOI 10.1002/ijgo.14411

  View details for PubMedID 35976039

• Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Frey, M. K., Ahsan, M. D., Bergeron, H., Lin, J., Li, X., Fowlkes, R. K., Narayan, P., Nitecki, R., Rauh-Hain, J. A., Moss, H. A., Baltich Nelson, B., Thomas, C., Christos, P. J., Hamilton, J. G., Chapman-Davis, E., Cantillo, E., Holcomb, K., Kurian, A. W., Lipkin, S., Offit, K., Sharaf, R. N. 2022: JCO2200303

  Abstract

  Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic.We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis.Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50).Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.

  View details for DOI 10.1200/JCO.22.00303

  View details for PubMedID 35960887

• What are the considerations in patient selection and timing of risk-reducing mastectomy? Cleveland Clinic journal of medicine Pederson, H. J., Kurian, A. W., Al Hilli, Z. 2022; 89 (8): 442-444

  View details for DOI 10.3949/ccjm.89a.21114

  View details for PubMedID 35914935

• Genetic counselors' experience with reimbursement and patient out-of-pocket cost for multi-cancer gene panel testing for hereditary cancer syndromes. Journal of genetic counseling Weldon, C. B., Trosman, J. R., Liang, S. Y., Douglas, M. P., Scheuner, M. T., Kurian, A., Schaa, K. L., Roscow, B., Erwin, D., Phillips, K. A. 2022

  Abstract

  Multi-cancer gene panels for hereditary cancer syndromes (hereditary cancer panels, HCPs) are widely available, and some laboratories have programs that limit patients' out-of-pocket (OOP) cost share. However, little is known about practices by cancer genetic counselors for discussing and ordering an HCP and how insurance reimbursement and patient out-of-pocket share impact these practices. We conducted a survey of cancer genetic counselors based in the United States through the National Society of Genetic Counselors to assess the impact of reimbursement and patient OOP share on ordering of an HCP and hereditary cancer genetic counseling. Data analyses were conducted using chi-square and t tests. We received 135 responses (16% response rate). We found that the vast majority of respondents (94%, 127/135) ordered an HCP for patients rather than single-gene tests to assess hereditary cancer predisposition. Two-thirds of respondents reported that their institution had no protocol related to discussing HCPs with patients. Most respondents (84%, 114/135) indicated clinical indications and patients' requests as important in selecting and ordering HCPs, while 42%, 57/135, considered reimbursement and patient OOP share factors important. We found statistically significant differences in reporting of insurance as a frequently used payment method for HCPs and in-person genetic counseling (84% versus 59%, respectively, p < 0.0001). Perceived patient willingness to pay more than $100 was significantly higher for HCPs than for genetic counseling(41% versus 22%, respectively, p < 0.01). In sum, genetic counselors' widespread selection and ordering of HCPs is driven more by clinical indications and patient preferences than payment considerations. Respondents perceived that testing is more often reimbursed by insurance than genetic counseling, and patients are more willing to pay for an HCP than for genetic counseling. Policy efforts should address this incongruence in reimbursement and patient OOP share. Patient-centered communication should educate patients on the benefit of genetic counseling.

  View details for DOI 10.1002/jgc4.1614

  View details for PubMedID 35900261

• Examining Associations Among Sexual Health, Unmet Care Needs, and Distress in Breast and Gynecologic Cancer Survivors. Seminars in oncology nursing Benedict, C., Fisher, S., Kumar, D., Pollom, E., Schapira, L., Kurian, A. W., Berek, J. S., Palesh, O. 2022: 151316

  Abstract

  This study evaluated breast and gynecologic cancer patients' sexual function, unmet needs related to sexuality, and distress.Secondary analyses of a cross-sectional survey study evaluated measures of sexual function (Female Sexual Function Index [FSFI]), unmet needs (Supportive Care Needs Scale), and distress (Patient Health Questionnaire). χ2 test, t tests, and analysis of variances (ANOVAs) tested bivariate relationships. Subgroup comparisons were made based on the Female Sexual Function Index sexual dysfunction diagnostic cut-off score (<26.55; lower scores indicate greater dysfunction). A regression model tested associations between sexual function and unmet needs with distress as the outcome variable.Clinically significant sexual dysfunction was common in this cohort of women. In multivariate modeling, worse sexual function and greater unmet sexuality needs related to greater distress. Future work should explore reasons behind the high levels of sexual dysfunction and unmet needs in female survivors.It is important to routinely screen for sexual health concerns among female cancer survivors at all phases of the cancer trajectory including years posttreatment.

  View details for DOI 10.1016/j.soncn.2022.151316

  View details for PubMedID 35902337

• Symptoms and survivorship needs differences between "good sleepers" and "bad sleepers" in survivors of breast and gynecologic cancers. Sleep medicine Palesh, O., Tolby, L. T., Hofmeister, E. N., Fisher, S., Solomon, N. L., Sackeyfio, S., Berek, J. S., Kurian, A. W., Cassidy-Eagle, E., Schapira, L. 2022; 100: 49-55

  Abstract

  Although 80% of cancer survivors report symptoms of insomnia, only 28-43% meet DSM-5 criteria for this diagnosis. We sought to characterize the association between patient-reported insomnia symptoms, patient outcomes, and supportive care variables, as well as explore clinically meaningful insomnia thresholds in a sample of women diagnosed with breast and gynecologic cancers.From July 2018-March 2019, all breast and gynecologic cancer survivors seen at the Stanford Women's Cancer Center were approached and invited to participate in the study (15% declined). Of those who consented, 273 survivors completed an online survey related to their sleep (ISI), quality of life (FACT-G), distress (PHQ-4), supportive care needs (SCNS-SF34), and symptom severity (MDASI). Survivors who scored <8 on ISI were categorized as "good sleepers," survivors with ISI ≥8 were categorized as "bad sleepers."126 (46.2%) of survivors were "good sleepers," 147 (53.8%) were "bad sleepers." Good sleepers were older than bad sleepers (p < .05) but did not differ in any other demographic or any medical variables. Using hierarchical linear regression models, we found that good sleep (ISI <8) was associated with higher quality of life, lower psychological distress, increased social support, lower symptom severity, and lower supportive care needs, after accounting for demographic, medical, and treatment variables. The findings were largely replicated with an ISI cut off of 15.Among women treated for breast and gynecologic cancers, survivors who were good sleepers had better psychosocial outcomes, fewer supportive care needs, and lower symptom severity compared to those who reported insomnia symptoms. Results also indicate that degree of sleep impairment, whether mild or severe, has similarly poor associations with most aspects of patient functioning and symptomatic burden. Further research is needed to determine causality of these findings.

  View details for DOI 10.1016/j.sleep.2022.07.002

  View details for PubMedID 36007431

• Adherence to the 2020 American Cancer Society Guideline for Cancer Prevention and risk of breast cancer for women at increased familial and genetic risk in the Breast Cancer Family Registry: an evaluation of the weight, physical activity, and alcohol consumption recommendations. Breast cancer research and treatment Geczik, A. M., Ferris, J. S., Terry, M. B., Andrulis, I. L., Buys, S. S., Daly, M. B., Hopper, J. L., John, E. M., Kurian, A. W., Southey, M. C., Liao, Y., Genkinger, J. M. 2022

  Abstract

  The American Cancer Society (ACS) published an updated Guideline for Cancer Prevention (ACS Guideline) in 2020. Research suggests that adherence to the 2012 ACS Guideline might lower breast cancer risk, but there is limited evidence that this applies to women at increased familial and genetic risk of breast cancer.Using the Breast Cancer Family Registry (BCFR), a cohort enriched for increased familial and genetic risk of breast cancer, we examined adherence to three 2020 ACS Guideline recommendations (weight management (body mass index), physical activity, and alcohol consumption) with breast cancer risk in 9615 women. We used Cox proportional hazard regression modeling to calculate hazard ratios (HRs) and 95% confidence intervals (CI) overall and stratified by BRCA1 and BRCA2 pathogenic variant status, family history of breast cancer, menopausal status, and estrogen receptor-positive (ER +) breast cancer.We observed 618 incident invasive or in situ breast cancers over a median 12.9 years. Compared with being adherent to none (n = 55 cancers), being adherent to any ACS recommendation (n = 563 cancers) was associated with a 27% lower breast cancer risk (HR = 0.73, 95% CI: 0.55-0.97). This was evident for women with a first-degree family history of breast cancer (HR = 0.68, 95% CI: 0.50-0.93), women without BRCA1 or BRCA2 pathogenic variants (HR = 0.71, 95% CI: 0.53-0.95), postmenopausal women (HR = 0.63, 95% CI: 0.44-0.89), and for risk of ER+ breast cancer (HR = 0.63, 95% CI: 0.40-0.98).Adherence to the 2020 ACS Guideline recommendations for BMI, physical activity, and alcohol consumption could reduce breast cancer risk for postmenopausal women and women at increased familial risk.

  View details for DOI 10.1007/s10549-022-06656-7

  View details for PubMedID 35780210

• Chemotherapy Regimens Received by Women with BRCA1/2 Pathogenic Variants for Early-Stage Breast Cancer Treatment. JNCI cancer spectrum Kurian, A. W., Abrahamse, P., Hamilton, A. S., Caswell-Jin, J. L., Gomez, S. L., Hofer, T. J., Ward, K. C., Katz, S. J. 2022

  Abstract

  Genetic testing is widespread among breast cancer patients; however, no guideline recommends using germline genetic testing results to select a chemotherapy regimen. It is unknown whether breast cancer patients who carry pathogenic variants (PVs) in BRCA1/2 or other cancer-associated genes receive different chemotherapy regimens than non-carriers.We linked Surveillance, Epidemiology and End Results (SEER) registry records from Georgia and California to germline genetic testing results from four clinical laboratories. Patients were included who: 1) had stages I-III breast cancer, either hormone receptor-positive and HER2-negative (HR-positive/HER2-negative) or triple-negative (TNBC), diagnosed in 2013-2017; 2) received chemotherapy; and 3) linked to genetic results. Chemotherapy details were extracted from SEER text fields completed by registrars. We examined whether PV carriers received more intensive regimens (HR-positive, HER2-negative: ≥3 drugs including an anthracycline; TNBC: ≥4 drugs including an anthracycline and platinum) and/or less standard breast cancer agents (a platinum). All statistical tests were 2-sided.Among 2,293 patients, 1,451 had HR-positive/HER2-negative disease and 842 had TNBC. On multivariable analysis of women with HR-positive/HER2-negative disease, receipt of a more intensive chemotherapy regimen varied significantly by genetic results (p=.02), with platinum receipt more common among BRCA1/2 PV carriers (odds ratio 2.44, 95% confidence interval 1.36-4.38, p<.001). Among women with TNBC, chemotherapy agents did not vary significantly by genetic results.BRCA1/2 PV carriers with HR-positive/HER2-negative breast cancer had two-fold higher odds than non-carriers of receiving a platinum, as part of a more intensive chemotherapy regimen. This likely represents over-treatment and emphasizes the need to monitor how genetic testing results are managed in oncology practice.

  View details for DOI 10.1093/jncics/pkac045

  View details for PubMedID 35723570

• Association of illness mindsets with health-related quality of life in cancer survivors. Health psychology : official journal of the Division of Health Psychology, American Psychological Association Zeidman, A., Benedict, C., Zion, S. R., Fisher, S., Tolby, L., Kurian, A. W., Berek, J. S., Woldeamanuel, Y. W., Schapira, L., Palesh, O. 2022; 41 (6): 389-395

  Abstract

  This study aimed to examine the association between mindsets-established, but mutable beliefs that a person holds-and health-related quality of life in survivors of breast and gynecologic cancer.A cross-sectional survey study was conducted with breast and gynecologic cancer survivors. Measures included the Illness Mindset Questionnaire and Functional Assessment of Cancer Therapy-General (FACT-G).Two hundred seventy-three survivors (74% breast/26% gynecologic) who were on average 3.9 years post-diagnosis (SD = 4.2), Mage 55 (SD = 12) completed the survey (response rate 80%). Of the survivors, 20.1% (N = 55) endorsed ("agree" or "strongly agree") that Cancer is a Catastrophe, 52.4% (N = 143) endorsed that Cancer is Manageable, and 65.9% (N = 180) endorsed that Cancer can be an Opportunity (not mutually exclusive). Those who endorsed a maladaptive mindset (Cancer is a Catastrophe) reported lower health-related quality of life (HRQOL) compared with those who did not hold this belief (p < .001). Alternatively, those who endorsed more adaptive mindsets (Cancer is Manageable or Cancer can be an Opportunity) reported better HRQOL compared with those who disagreed (all p-values < .05). All three mindsets were independent correlates of HRQOL, explaining 6-15% unique variance in HRQOL, even after accounting for demographic and medical factors.Mindsets about illness are significantly associated with HRQOL in cancer survivors. Our data come from a one-time evaluation of cancer survivors at a single clinic and provide a foundation for future longitudinal studies and RCTs on the relationship between mindsets and psychosocial outcomes in cancer survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

  View details for DOI 10.1037/hea0001186

  View details for PubMedID 35604702

• Constitutional BRCA1 methylation and risk of incident triple-negative breast cancer and high-grade serous ovarian cancer. Lonning, P., Nikolaienko, O., Pan, K., Kurian, A. W., Eikesdal, H., Pettinger, M., Anderson, G. L., Prentice, R. L., Chlebowski, R. T., Knappskog, S. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300121

• A case-control study of healthcare disparities in sex and gender minority patients with breast cancer. Eckhert, E., Lansinger, O., Liu, M., Purington, N., Han, S. S., Schapira, L., Sledge, G. W., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680301817

• Radiomic features quantifying pixel-level characteristics of breast tumors from magnetic resonance imaging predict risk factors in triple-negative breast cancer. Mantz, A. B., Zhou, R., Kozlov, A., DeMartini, W., Chen, S., Okamoto, S., Ikeda, D. M., Mattonen, S. A., Napel, S., Alkim, E., Sledge, G. W., Kurian, A. W., Liu, M., Telli, M. L., Itakura, H. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680302515

• Harnessing artificial intelligence to automate delineation of volumetric breast cancers from magnetic resonance imaging to improve tumor characterization. Zhou, R., Kozlov, A., Chen, S., Okamoto, S., Ikeda, D. M., DeMartini, W., Kurian, A. W., Sledge, G. W., Telli, M. L., Lee, K., Mantz, A. B., Itakura, H. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680301695

• Contributions of screening, early-stage treatment, and metastatic treatment to breast cancer mortality reduction by molecular subtype in US women, 2000-2017. Caswell-Jin, J., Sun, L., Munoz, D., Lu, Y., Li, Y., Huang, H., Hampton, J. M., Song, J., Jayasekera, J., Schechter, C., Alagoz, O., Stout, N. K., Trentham-Dietz, A., Mandelblatt, J. S., Berry, D. A., Lee, S. J., Huang, X., Kurian, A. W., Plevritis, S. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300063

• Ancestry-specific risk of triple-negative breast cancer (TNBC) associated with germline pathogenic variants (PV) in hereditary cancer (CA) predisposition genes. Hall, M. J., Hughes, E., Kucera, M., Kidd, J., Bernhisel, R., Hullinger, B., Slavin, T., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300130

• Simulation modeling as a tool to support clinical guidelines and care for breast cancer prevention and early detection in high-risk women. Jayasekera, J., Lowry, K. P., Yeh, J. M., Schwartz, M. D., Wernli, K. J., Isaacs, C., Kurian, A. W., Stout, N. K. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300138

• A pilot study to increase cascade genetic testing in families with hereditary cancer syndromes. Katz, S. J., Tocco, R., Hawley, S. T., An, L., Hodan, R., Ward, K. C., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300221

• Association of germline genetic testing results with chemotherapy regimens received by women with early-stage breast cancer. Kurian, A. W., Abrahamse, P., Caswell Jin, J., Hamilton, A. S., Hofer, T., Ward, K. C., Katz, S. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300131

• National claims data analysis of outcomes of hospitalized cancer patients without COVID-19 infection during versus prior to the COVID-19 pandemic. Caswell-Jin, J., Shafaee, M., Liu, M., Xiao, L., John, E. M., Bondy, M., Kurian, A. W. LIPPINCOTT WILLIAMS & WILKINS. 2022: E18679

  View details for Web of Science ID 000863680303824

• Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial. Cancers Archer, S., Fennell, N., Colvin, E., Laquindanum, R., Mills, M., Dennis, R., Stutzin Donoso, F., Gold, R., Fan, A., Downes, K., Ford, J., Antoniou, A. C., Kurian, A. W., Evans, D. G., Tischkowitz, M. 2022; 14 (11)

  Abstract

  Women who test positive for an inherited pathogenic/likely pathogenic gene variant in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer-specifically breast (all) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). Women receive broad cancer risk figures that are not personalised (e.g., 44-63% lifetime risk of breast cancer for those with PALB2). Broad, non-personalised risk estimates may be problematic for women when they are considering how to manage their risk. Multifactorial-risk-prediction tools have the potential to deliver personalised risk estimates. These may be useful in the patient's decision-making process and impact uptake of risk-management options. This randomised control trial (registration number to follow), based in genetic centres in the UK and US, will randomise participants on a 1:1 basis to either receive conventional cancer risk estimates, as per routine clinical practice, or to receive a personalised risk estimate. This personalised risk estimate will be calculated using the CanRisk risk prediction tool, which combines the patient's genetic result, family history and polygenic risk score (PRS), along with hormonal and lifestyle factors. Women's decision-making around risk management will be monitored using questionnaires, completed at baseline (pre-appointment) and follow-up (one, three and twelve months after receiving their risk assessment). The primary outcome for this study is the type and timing of risk management options (surveillance, chemoprevention, surgery) taken up over the course of the study (i.e., 12 months). The type of risk-management options planned to be taken up in the future (i.e., beyond the end of the study) and the potential impact of personalised risk estimates on women's psychosocial health will be collected as secondary-outcome measures. This study will also assess the acceptability, feasibility and cost-effectiveness of using personalised risk estimates in clinical care.

  View details for DOI 10.3390/cancers14112716

  View details for PubMedID 35681696

• Breast cancer diagnosis and treatment during the COVID-19 pandemic in a nationwide, insured population. Breast cancer research and treatment Caswell-Jin, J. L., Shafaee, M. N., Xiao, L., Liu, M., John, E. M., Bondy, M. L., Kurian, A. W. 2022

  Abstract

  The early months of the COVID-19 pandemic led to reduced cancer screenings and delayed cancer surgeries. We used insurance claims data to understand how breast cancer incidence and treatment after diagnosis changed nationwide over the course of the pandemic.Using the Optum Research Database from January 2017 to March 2021, including approximately 19 million US adults with commercial health insurance, we identified new breast cancer diagnoses and first treatment after diagnosis. We compared breast cancer incidence and proportion of newly diagnosed patients receiving pre-operative systemic therapy pre-COVID, in the first 2 months of the COVID pandemic and in the later part of the COVID pandemic.Average monthly breast cancer incidence was 19.3 (95% CI 19.1-19.5) cases per 100,000 women and men pre-COVID, 11.6 (95% CI 10.8-12.4) per 100,000 in April-May 2020, and 19.7 (95% CI 19.3-20.1) per 100,000 in June 2020-February 2021. Use of pre-operative systemic therapy was 12.0% (11.7-12.4) pre-COVID, 37.7% (34.9-40.7) for patients diagnosed March-April 2020, and 14.8% (14.0-15.7) for patients diagnosed May 2020-January 2021. The changes in breast cancer incidence across the pandemic did not vary by demographic factors. Use of pre-operative systemic therapy across the pandemic varied by geographic region, but not by area socioeconomic deprivation or race/ethnicity.In this US-insured population, the dramatic changes in breast cancer incidence and the use of pre-operative systemic therapy experienced in the first 2 months of the pandemic did not persist, although a modest change in the initial management of breast cancer continued.

  View details for DOI 10.1007/s10549-022-06634-z

  View details for PubMedID 35624175

• Relevance of the MHC region for breast cancer susceptibility in Asians. Breast cancer (Tokyo, Japan) Ho, P. J., Khng, A. J., Tan, B. K., Tan, E. Y., Tan, S. M., Tan, V. K., Lim, G. H., Aronson, K. J., Chan, T. L., Choi, J. Y., Dennis, J., Ho, W. K., Hou, M. F., Ito, H., Iwasaki, M., John, E. M., Kang, D., Kim, S. W., Kurian, A. W., Kwong, A., Lophatananon, A., Matsuo, K., Mohd-Taib, N. A., Muir, K., Murphy, R. A., Park, S. K., Shen, C. Y., Shu, X. O., Teo, S. H., Wang, Q., Yamaji, T., Zheng, W., Bolla, M. K., Dunning, A. M., Easton, D. F., Pharoah, P. D., Hartman, M., Li, J. 2022

  Abstract

  Human leukocyte antigen (HLA) genes play critical roles in immune surveillance, an important defence against tumors. Imputing HLA genotypes from existing single-nucleotide polymorphism datasets is low-cost and efficient. We investigate the relevance of the major histocompatibility complex region in breast cancer susceptibility, using imputed class I and II HLA alleles, in 25,484 women of Asian ancestry.A total of 12,901 breast cancer cases and 12,583 controls from 12 case-control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15-55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined.We did not observe associations between any HLA allele and breast cancer risk at P < 5e-8; the smallest p value was observed for HLA-C*12:03 (OR = 1.29, P = 1.08e-3). Ninety-five percent of the effect sizes (OR) observed were between 0.90 and 1.23. Similar results were observed when different subtypes of breast cancer were studied (95% of ORs were between 0.85 and 1.18).No imputed HLA allele was associated with breast cancer risk in our large Asian study. Direct measurement of HLA gene expressions may be required to further explore the associations between HLA genes and breast cancer risk.

  View details for DOI 10.1007/s12282-022-01366-w

  View details for PubMedID 35543923

• Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci. Breast cancer research : BCR Chen, H., Fan, S., Stone, J., Thompson, D. J., Douglas, J., Li, S., Scott, C., Bolla, M. K., Wang, Q., Dennis, J., Michailidou, K., Li, C., Peters, U., Hopper, J. L., Southey, M. C., Nguyen-Dumont, T., Nguyen, T. L., Fasching, P. A., Behrens, A., Cadby, G., Murphy, R. A., Aronson, K., Howell, A., Astley, S., Couch, F., Olson, J., Milne, R. L., Giles, G. G., Haiman, C. A., Maskarinec, G., Winham, S., John, E. M., Kurian, A., Eliassen, H., Andrulis, I., Evans, D. G., Newman, W. G., Hall, P., Czene, K., Swerdlow, A., Jones, M., Pollan, M., Fernandez-Navarro, P., McConnell, D. S., Kristensen, V. N., Rothstein, J. H., Wang, P., Habel, L. A., Sieh, W., Dunning, A. M., Pharoah, P. D., Easton, D. F., Gierach, G. L., Tamimi, R. M., Vachon, C. M., Lindström, S. 2022; 24 (1): 27

  Abstract

  Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants.We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia.We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes.Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.

  View details for DOI 10.1186/s13058-022-01524-0

  View details for PubMedID 35414113

• Trends in Annual Surveillance Mammography Participation Among Breast Cancer Survivors From 2004 to 2016. Journal of the National Comprehensive Cancer Network : JNCCN Lowry, K. P., Callaway, K. A., Lee, J. M., Zhang, F., Ross-Degnan, D., Wharam, J. F., Kerlikowske, K., Wernli, K. J., Kurian, A. W., Henderson, L. M., Stout, N. K. 2022; 20 (4): 379-386.e9

  Abstract

  Annual mammography is recommended for breast cancer survivors; however, population-level temporal trends in surveillance mammography participation have not been described. Our objective was to characterize trends in annual surveillance mammography participation among women with a personal history of breast cancer over a 13-year period.We examined annual surveillance mammography participation from 2004 to 2016 in a nationwide sample of commercially insured women with prior breast cancer. Rates were stratified by age group (40-49 vs 50-64 years), visit with a surgical/oncology specialist or primary care provider within the prior year, and sociodemographic characteristics. Joinpoint models were used to estimate annual percentage changes (APCs) in participation during the study period.Among 141,672 women, mammography rates declined from 74.1% in 2004 to 67.1% in 2016. Rates were stable from 2004 to 2009 (APC, 0.1%; 95% CI, -0.5% to 0.8%) but declined 1.5% annually from 2009 to 2016 (95% CI, -1.9% to -1.1%). For women aged 40 to 49 years, rates declined 2.8% annually (95% CI, -3.4% to -2.1%) after 2009 versus 1.4% annually in women aged 50 to 64 years (95% CI, -1.9% to -1.0%). Similar trends were observed in women who had seen a surgeon/oncologist (APC, -1.7%; 95% CI, -2.1% to -1.4%) or a primary care provider (APC, -1.6%; 95% CI, -2.1% to -1.2%) in the prior year.Surveillance mammography participation among breast cancer survivors declined from 2009 to 2016, most notably among women aged 40 to 49 years. These findings highlight a need for focused efforts to improve adherence to surveillance and prevent delays in detection of breast cancer recurrence and second cancers.

  View details for DOI 10.6004/jnccn.2021.7081

  View details for PubMedID 35390766

• Clinician-Reported Impact of Germline Multigene Panel Testing on Cancer Risk Management Recommendations. JNCI cancer spectrum Horton, C., Blanco, K., Lo, M. T., Speare, V., LaDuca, H., Dolinsky, J. S., Kurian, A. W. 2022; 6 (2)

  Abstract

  With increased adoption of multi-gene panel testing (MGPT) for hereditary cancer, management guidelines now include a wider range of predisposition genes. Yet little is known about whether MGPT results prompt changes to clinicians' risk management recommendations and whether those recommendations adhere to guidelines.We assessed cancer risk management recommendations made by clinicians ordering MGPT for hereditary cancer at a diagnostic laboratory using an internet-based survey. We received paired pre- and posttest responses for 2172 patients (response rate = 14.3%). Unpaired posttest responses were received in 168 additional patients with positive results. All tests were 2-sided.Clinicians reported a change in risk management recommendations for 76.6% of patients who tested positive for a pathogenic or likely pathogenic variant, with changes to surveillance being most common (71.1%), followed by surgical (33.6%), chemoprevention (15.1%), and clinical trial (9.4%) recommendations. Clinicians recommended risk-reducing interventions more often for patients with pathogenic variants in high-risk than moderate-risk genes (P < .001), whereas surveillance recommendations were similar for high-risk and moderate-risk genes. Guideline adherence was high for surveillance (86.3%) and surgical (79.6%) recommendations. Changes to risk management recommendations occurred in 8.8% and 7.6% of patients with uncertain and negative results, respectively.Clinicians report frequent changes to cancer risk management recommendations based on positive results in both high-risk and moderate-risk genes. Reported introduction of interventions in patients with inconclusive and negative results is rare and adherence to practice guidelines is high in patients with positive results, suggesting a low probability of harm resulting from MGPT.

  View details for DOI 10.1093/jncics/pkac002

  View details for PubMedID 35603838

• Risk-reducing salpingo-oophorectomy consults and practices during the COVID-19 pandemic Gynecologic Oncology Reports O'Mara, A. E., Benedict, C., Kurian, A. W., Wagner, S. K., Diver, E. J. 2022

  View details for DOI 10.1016/j.gore.2022.101036

• Polygenic risk modeling for prediction of epithelial ovarian cancer risk. European journal of human genetics : EJHG Dareng, E. O., Tyrer, J. P., Barnes, D. R., Jones, M. R., Yang, X., Aben, K. K., Adank, M. A., Agata, S., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Aravantinos, G., Arun, B. K., Augustinsson, A., Balmaña, J., Bandera, E. V., Barkardottir, R. B., Barrowdale, D., Beckmann, M. W., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Bernardini, M. Q., Bjorge, L., Black, A., Bogdanova, N. V., Bonanni, B., Borg, A., Brenton, J. D., Budzilowska, A., Butzow, R., Buys, S. S., Cai, H., Caligo, M. A., Campbell, I., Cannioto, R., Cassingham, H., Chang-Claude, J., Chanock, S. J., Chen, K., Chiew, Y. E., Chung, W. K., Claes, K. B., Colonna, S., Cook, L. S., Couch, F. J., Daly, M. B., Dao, F., Davies, E., de la Hoya, M., de Putter, R., Dennis, J., DePersia, A., Devilee, P., Diez, O., Ding, Y. C., Doherty, J. A., Domchek, S. M., Dörk, T., du Bois, A., Dürst, M., Eccles, D. M., Eliassen, H. A., Engel, C., Evans, G. D., Fasching, P. A., Flanagan, J. M., Fortner, R. T., Machackova, E., Friedman, E., Ganz, P. A., Garber, J., Gensini, F., Giles, G. G., Glendon, G., Godwin, A. K., Goodman, M. T., Greene, M. H., Gronwald, J., Hahnen, E., Haiman, C. A., Håkansson, N., Hamann, U., Hansen, T. V., Harris, H. R., Hartman, M., Heitz, F., Hildebrandt, M. A., Høgdall, E., Høgdall, C. K., Hopper, J. L., Huang, R. Y., Huff, C., Hulick, P. J., Huntsman, D. G., Imyanitov, E. N., Isaacs, C., Jakubowska, A., James, P. A., Janavicius, R., Jensen, A., Johannsson, O. T., John, E. M., Jones, M. E., Kang, D., Karlan, B. Y., Karnezis, A., Kelemen, L. E., Khusnutdinova, E., Kiemeney, L. A., Kim, B. G., Kjaer, S. K., Komenaka, I., Kupryjanczyk, J., Kurian, A. W., Kwong, A., Lambrechts, D., Larson, M. C., Lazaro, C., Le, N. D., Leslie, G., Lester, J., Lesueur, F., Levine, D. A., Li, L., Li, J., Loud, J. T., Lu, K. H., Lubiński, J., Mai, P. L., Manoukian, S., Marks, J. R., Matsuno, R. K., Matsuo, K., May, T., McGuffog, L., McLaughlin, J. R., McNeish, I. A., Mebirouk, N., Menon, U., Miller, A., Milne, R. L., Minlikeeva, A., Modugno, F., Montagna, M., Moysich, K. B., Munro, E., Nathanson, K. L., Neuhausen, S. L., Nevanlinna, H., Yie, J. N., Nielsen, H. R., Nielsen, F. C., Nikitina-Zake, L., Odunsi, K., Offit, K., Olah, E., Olbrecht, S., Olopade, O. I., Olson, S. H., Olsson, H., Osorio, A., Papi, L., Park, S. K., Parsons, M. T., Pathak, H., Pedersen, I. S., Peixoto, A., Pejovic, T., Perez-Segura, P., Permuth, J. B., Peshkin, B., Peterlongo, P., Piskorz, A., Prokofyeva, D., Radice, P., Rantala, J., Riggan, M. J., Risch, H. A., Rodriguez-Antona, C., Ross, E., Rossing, M. A., Runnebaum, I., Sandler, D. P., Santamariña, M., Soucy, P., Schmutzler, R. K., Setiawan, V. W., Shan, K., Sieh, W., Simard, J., Singer, C. F., Sokolenko, A. P., Song, H., Southey, M. C., Steed, H., Stoppa-Lyonnet, D., Sutphen, R., Swerdlow, A. J., Tan, Y. Y., Teixeira, M. R., Teo, S. H., Terry, K. L., Terry, M. B., Thomassen, M., Thompson, P. J., Thomsen, L. C., Thull, D. L., Tischkowitz, M., Titus, L., Toland, A. E., Torres, D., Trabert, B., Travis, R., Tung, N., Tworoger, S. S., Valen, E., van Altena, A. M., van der Hout, A. H., Van Nieuwenhuysen, E., van Rensburg, E. J., Vega, A., Edwards, D. V., Vierkant, R. A., Wang, F., Wappenschmidt, B., Webb, P. M., Weinberg, C. R., Weitzel, J. N., Wentzensen, N., White, E., Whittemore, A. S., Winham, S. J., Wolk, A., Woo, Y. L., Wu, A. H., Yan, L., Yannoukakos, D., Zavaglia, K. M., Zheng, W., Ziogas, A., Zorn, K. K., Kleibl, Z., Easton, D., Lawrenson, K., DeFazio, A., Sellers, T. A., Ramus, S. J., Pearce, C. L., Monteiro, A. N., Cunningham, J., Goode, E. L., Schildkraut, J. M., Berchuck, A., Chenevix-Trench, G., Gayther, S. A., Antoniou, A. C., Pharoah, P. D. 2022

  Abstract

  Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

  View details for DOI 10.1038/s41431-021-00987-7

  View details for PubMedID 35027648

• Rare germline copy number variants (CNVs) and breast cancer risk. Communications biology Dennis, J., Tyrer, J. P., Walker, L. C., Michailidou, K., Dorling, L., Bolla, M. K., Wang, Q., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Freeman, L. E., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N. V., Bojesen, S. E., Brenner, H., Castelao, J. E., Chang-Claude, J., Chenevix-Trench, G., Clarke, C. L., Collée, J. M., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Devilee, P., Dörk, T., Dossus, L., Eliassen, A. H., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Fletcher, O., Flyger, H., Fritschi, L., Gabrielson, M., Gago-Dominguez, M., García-Closas, M., Giles, G. G., González-Neira, A., Guénel, P., Hahnen, E., Haiman, C. A., Hall, P., Hollestelle, A., Hoppe, R., Hopper, J. L., Howell, A., Jager, A., Jakubowska, A., John, E. M., Johnson, N., Jones, M. E., Jung, A., Kaaks, R., Keeman, R., Khusnutdinova, E., Kitahara, C. M., Ko, Y. D., Kosma, V. M., Koutros, S., Kraft, P., Kristensen, V. N., Kubelka-Sabit, K., Kurian, A. W., Lacey, J. V., Lambrechts, D., Larson, N. L., Linet, M., Ogrodniczak, A., Mannermaa, A., Manoukian, S., Margolin, S., Mavroudis, D., Milne, R. L., Muranen, T. A., Murphy, R. A., Nevanlinna, H., Olson, J. E., Olsson, H., Park-Simon, T. W., Perou, C. M., Peterlongo, P., Plaseska-Karanfilska, D., Pylkäs, K., Rennert, G., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schmidt, M. K., Schmutzler, R. K., Shibli, R., Smeets, A., Soucy, P., Southey, M. C., Swerdlow, A. J., Tamimi, R. M., Taylor, J. A., Teras, L. R., Terry, M. B., Tomlinson, I., Troester, M. A., Truong, T., Vachon, C. M., Wendt, C., Winqvist, R., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Simard, J., Dunning, A. M., Pharoah, P. D., Easton, D. F. 2022; 5 (1): 65

  Abstract

  Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

  View details for DOI 10.1038/s42003-021-02990-6

  View details for PubMedID 35042965

• Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast cancer research : BCR Ahearn, T. U., Zhang, H., Michailidou, K., Milne, R. L., Bolla, M. K., Dennis, J., Dunning, A. M., Lush, M., Wang, Q., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Auer, P. L., Augustinsson, A., Baten, A., Becher, H., Behrens, S., Benitez, J., Bermisheva, M., Blomqvist, C., Bojesen, S. E., Bonanni, B., Børresen-Dale, A. L., Brauch, H., Brenner, H., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S. S., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Chenevix-Trench, G., Clarke, C. L., Collée, J. M., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dörk, T., Dwek, M., Eccles, D. M., Evans, D. G., Fasching, P. A., Figueroa, J., Floris, G., Gago-Dominguez, M., Gapstur, S. M., García-Sáenz, J. A., Gaudet, M. M., Giles, G. G., Goldberg, M. S., González-Neira, A., Alnæs, G. I., Grip, M., Guénel, P., Haiman, C. A., Hall, P., Hamann, U., Harkness, E. F., Heemskerk-Gerritsen, B. A., Holleczek, B., Hollestelle, A., Hooning, M. J., Hoover, R. N., Hopper, J. L., Howell, A., Jakimovska, M., Jakubowska, A., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Kauppila, S., Keeman, R., Khusnutdinova, E., Kitahara, C. M., Ko, Y. D., Koutros, S., Kristensen, V. N., Krüger, U., Kubelka-Sabit, K., Kurian, A. W., Kyriacou, K., Lambrechts, D., Lee, D. G., Lindblom, A., Linet, M., Lissowska, J., Llaneza, A., Lo, W. Y., MacInnis, R. J., Mannermaa, A., Manoochehri, M., Margolin, S., Martinez, M. E., McLean, C., Meindl, A., Menon, U., Nevanlinna, H., Newman, W. G., Nodora, J., Offit, K., Olsson, H., Orr, N., Park-Simon, T. W., Patel, A. V., Peto, J., Pita, G., Plaseska-Karanfilska, D., Prentice, R., Punie, K., Pylkäs, K., Radice, P., Rennert, G., Romero, A., Rüdiger, T., Saloustros, E., Sampson, S., Sandler, D. P., Sawyer, E. J., Schmutzler, R. K., Schoemaker, M. J., Schöttker, B., Sherman, M. E., Shu, X. O., Smichkoska, S., Southey, M. C., Spinelli, J. J., Swerdlow, A. J., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Teras, L. R., Terry, M. B., Torres, D., Troester, M. A., Vachon, C. M., van Deurzen, C. H., van Veen, E. M., Wagner, P., Weinberg, C. R., Wendt, C., Wesseling, J., Winqvist, R., Wolk, A., Yang, X. R., Zheng, W., Couch, F. J., Simard, J., Kraft, P., Easton, D. F., Pharoah, P. D., Schmidt, M. K., García-Closas, M., Chatterjee, N. 2022; 24 (1): 2

  Abstract

  Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

  View details for DOI 10.1186/s13058-021-01484-x

  View details for PubMedID 34983606

• Genetic Insights Into Biological Mechanisms Governing Human Ovarian Ageing OBSTETRICAL & GYNECOLOGICAL SURVEY Ruth, K. S., Day, F. R., Hussain, J. 2021; 76 (11): 678-679

  View details for DOI 10.1097/01.ogx.0000800176.90737.65

  View details for Web of Science ID 000732787100013

• Multicancer hereditary syndrome testing: Genetic counselors' perspectives Weldon, C. B., Liang, S., Phillips, K. A., Douglas, M. P., Scheuner, M., Kurian, A. W., Schaa, K., Roscow, B., Erwin, D., Trosman, J. R. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.106

  View details for Web of Science ID 000707130200105

• The Impact of COVID-19 on Patients With Cancer: A National Study of Patient Experiences. American journal of clinical oncology Rodriguez, G. M., Ferguson, J. M., Kurian, A., Bondy, M., Patel, M. I. 2021

  Abstract

  OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic abruptly disrupted cancer care. The impact of these disruptions on patient experiences remain relatively understudied. The objective of this study was to assess patients' perspectives regarding the impact of COVID-19 on their experiences, including their cancer care, emotional and mental health, and social determinants of health, and to evaluate whether these outcomes differed by cancer stage.MATERIALS AND METHODS: We conducted a survey among adults with cancer across the United States from April 1, 2020 to August 26, 2020 using virtual snowball sampling strategy in collaboration with professional organizations, cancer care providers, and patient advocacy groups. We analyzed data using descriptive statistics, chi2 and t tests.RESULTS: Three hundred twelve people with cancer participated and represented 38 states. The majority were non-Hispanic White (n=183; 58.7%) and female (n=177; 56.7%) with median age of 57 years. Ninety-one percent spoke English at home, 70.1% had health insurance, and 67% had access to home internet. Breast cancer was the most common diagnosis (n=67; 21.5%). Most had Stage 4 disease (n=80; 25.6%). Forty-six percent (n=145) experienced a change in their care due to COVID-19. Sixty percent (n=187) reported feeling very or extremely concerned that the pandemic would affect their cancer and disproportionately experienced among those with advanced cancer stages compared with earlier stages (P<0.001). Fifty-two percent (n=162) reported impact of COVID-19 on 1 or more aspects of social determinants of health with disproportionate impact among those with advanced cancer stages compared with earlier stages.CONCLUSIONS: COVID-19 impacted the care and well-being of patients with cancer and this impact was more pronounced among people with advanced cancer stages. Future work should consider tailored interventions to mitigate the impact of COVID-19 on patients with cancer.

  View details for DOI 10.1097/COC.0000000000000865

  View details for PubMedID 34519677

• Development of a Mobile Health App (TOGETHERCare) to Reduce Cancer Care Partner Burden: Product Design Study. JMIR formative research Oakley-Girvan, I., Davis, S. W., Kurian, A., Rosas, L. G., Daniels, J., Palesh, O. G., Mesia, R. J., Kamal, A. H., Longmire, M., Divi, V. 2021; 5 (8): e22608

  Abstract

  Approximately 6.1 million adults in the United States serve as care partners for cancer survivors. Studies have demonstrated that engaging cancer survivors and their care partners through technology-enabled structured symptom collection has several benefits. Given the high utilization of mobile technologies, even among underserved populations and in low resource areas, mobile apps may provide a meaningful access point for all stakeholders for symptom management.We aimed to develop a mobile app incorporating user preferences to enable cancer survivors' care partners to monitor the survivors' health and to provide care partner resources.An iterative information gathering process was conducted that included (1) discussions with 138 stakeholders to identify challenges and gaps in survivor home care; (2) semistructured interviews with clinicians (n=3), cancer survivors (n=3), and care partners (n=3) to identify specific needs; and (3) a 28-day feasibility field test with seven care partners.Health professionals noted the importance of identifying early symptoms of adverse events. Survivors requested modules on medication, diet, self-care, reminders, and a version in Spanish. Care partners preferred to focus primarily on the patient's health and not their own. The app was developed incorporating quality-of-life surveys and symptom reporting, as well as resources on home survivor care. Early user testing demonstrated ease of use and app feasibility.TOGETHERCare, a novel mobile app, was developed with user input to track the care partner's health and report on survivor symptoms during home care. The following two clinical benefits emerged: (1) reduced anxiety among care partners who use the app and (2) the potential for identifying survivor symptoms noted by the care partner, which might prevent adverse events.ClinicalTrials.gov NCT04018677; https://clinicaltrials.gov/ct2/show/NCT04018677.

  View details for DOI 10.2196/22608

  View details for PubMedID 34398787

• Widening cancer care disparities in the adoption of telemedicine during COVID 19: who is left behind? Liang, S., Richardson, M., Chen, T., Colocci, N., Kurian, A., de Briun, M., Chan, C., Chan, J. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2021: S23

  View details for Web of Science ID 000687070800036

• Twenty-one-gene recurrence score (RS) in germline (g)CHEK2 mutation-associated versus sporadic breast cancers (BC): A multi-site case-control study. Afghahi, A., Marsh, S., Winchester, A., Gao, D., Parris, H., Axell, L., Ellisen, L. W., Hofstatter, E., Kurian, A. W., Wood, M., Zakalik, D., Mullin, C., Caswell-Jin, J., Borges, V. F., Tung, N. M. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for Web of Science ID 000708120605272

• A simulation model-based clinical decision tool to guide personalized treatment based on individual characteristics: Does 21-gene recurrence score assay testing change decisions? Jayasekera, J., Sparano, J. A., Chandler, Y., Isaacs, C., Kurian, A. W., Kushi, L. H., O'Neill, S. C., Schechter, C. B., Mandelblatt, J. S. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e12507

  View details for Web of Science ID 000708120300008

• Breast cancer screening for carriers of ATM, CHEK2, and PALB2 pathogenic variants: A comparative modeling analysis. Lowry, K. P., Geuzinge, H., Stout, N. K., Alagoz, O., Hampton, J. M., Kerlikowske, K., Miglioretti, D. L., Schecter, C., Sprague, B. L., Trentham-Dietz, A., Tosteson, A. A., Van Ravesteyn, N., Yaffe, M., Yeh, J., Couch, F., Kraft, P., Polley, E., Mandelblatt, J. S., Kurian, A. W., Robson, M. E., Canc Intervention Surveillance, Canc Risk Estimates Related LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for Web of Science ID 000708120605242

• Cancer-specific mortality associated with germline genetic testing results among women with breast cancer or ovarian cancer treated with chemotherapy. Kurian, A. W., Abrahamse, P., Hamilton, A. S., Deapen, D., Gomez, S., Morrow, M., Berek, J. S., Katz, S. J., Ward, K. C. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for Web of Science ID 000708120605258

• Impact of disruptions in breast cancer control due to the COVID-19 pandemic on breast cancer mortality in the United States: Estimates from collaborative simulation modeling. Alagoz, O., Lowry, K. P., Kurian, A. W., Mandelblatt, J. S., Ergun, M., Huang, H., Lee, S. J., Schecter, C., Tosteson, A. A., Miglioretti, D. L., Trentham-Dietz, A., Nyante, S., Kerlikowske, K., Sprague, B. L., Stout, N. K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.6562

  View details for Web of Science ID 000708120604016

• EXAMINING ASSOCIATIONS AMONG SEXUAL HEALTH, UNMET CARE NEEDS RELATED TO SEXUALITY, AND DISTRESS IN BREAST AND GYNECOLOGIC CANCER SURVIVORS Benedict, C., Fisher, S., Kuma, D., Pollom, E., Schapira, L., Kurian, A., Berek, J. S., Palesh, O. OXFORD UNIV PRESS INC. 2021: S605

  View details for Web of Science ID 000648922701433

• Financing of germline testing: implications for availability and access Lin, G., Scheuner, M., Trosman, J., Sales, P., Ackerman, S., Douglas, M., Weldon, C., Kurian, A., Phillips, K. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2021: S330-S331

  View details for Web of Science ID 000639219800501

• Multi-gene panel testing results prompt frequent and guideline adherent changes to cancer risk management recommendations based on clinician report Horton, C., LaDuca, H., Blanco, K., Lo, M., Speare, V., Dolinsky, J., Kurian, A. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2021: S51-S52

  View details for Web of Science ID 000639219800075

• ILLNESS MINDSETS, DEMOGRAPHIC AND MEDICAL FACTORS, AND HEALTH-RELATED QUALITY OF LIFE IN BREAST & GYNECOLOGIC CANCER SURVIVORS Zeidman, A., Benedict, C., Tolby, L., Zion, S., Fisher, S., Kurian, A. W., Berek, J. S., Woldeamanuel, Y., Schapira, L., Palesh, O. OXFORD UNIV PRESS INC. 2021: S266

  View details for Web of Science ID 000648922700539

• Benchmark Method for Cost Computations Across Health Care Systems: Cost of Care per Patient per Day in Breast Cancer Care. JCO oncology practice Blayney, D. W., Seto, T., Hoang, N., Lindquist, C., Kurian, A. W. 2021: OP2000462

  Abstract

  To estimate the value of cancer care and to compare value among episodes of care, a transparent, reproducible, and standardized cost computation methodology is needed. Charges, claims, and reimbursements are related to cost but are nontransparent and proprietary. We developed a method to measure the cost of the following phases of care: (1) initial treatment with curative intent, (2) surveillance and survivorship care, and (3) relapse and end-of-life care.We combined clinical data from our electronic health record, the state cancer registry, and the Social Security Death Index. We analyzed the care of patients with breast cancer and mapped Common Procedural Terminology (CPT) codes to the corresponding cost conversion factor and date in the CMS Medicare fee schedule. To account for varying duration of episodes of care, we computed a cost of care per day (CCPD) for each patient.Median CCPD for initial treatment was $29.45 in US dollars (USD), the CCPD for surveillance and survivorship care was $2.45 USD, and the CCPD for relapse care was $13.80 USD. Among the three breast cancer types (hormone receptor-positive or human epidermal growth factor receptor 2 [HER2]-negative, HER2-positive, and triple-negative), there was no difference in CCPD. Relapsed patients in the most expensive surveillance CCPD group had significantly shorter survival.We developed a method to identify high-value oncology care-cost of care per patient per day (CCPD)-in episodes of initial, survivorship, and relapse care. The methodology can help identify positive deviants (who have developed best practices) delivering high-value care. Merging our data with claims data from third-party payers can increase the accuracy and validity of the CCPD.

  View details for DOI 10.1200/OP.20.00462

  View details for PubMedID 33646822

• Impact of COVID-19 on breast cancer care at a Bay Area academic center Wu, J., Bobo, S., Henry, S., Mills, M., Kurian, A., Dirbas, F. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737701065

• Incident comorbidities in a diverse cohort of women treated for early-stage, hormone receptor-positive breast cancer Gupta, T., Purington, N., Liu, M., Han, S., Sledge, G., Schapira, L., Kurian, A. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737701241

• Trends in genetic testing and results for women diagnosed with breast cancer or ovarian cancer, 2013-2017 Kurian, A. W., Morrow, M., Katz, S. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737700112

• Development of a breast cancer risk assessment model for ATM mutation carriers incorporating tyrer-cuzick and a polygenic risk score (PRS) Gallagher, S., Hughes, E., Rosenthal, E., Kurian, A. W., Domchek, S., Garber, J., Probst, B., Morris, B., Tshiaba, P., Roa, B., Slavin, T. P., Wagner, S., Weitzel, J. N., Gutin, A., Lanchbury, J. S., Robson, M. E. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737700120

• Triple-negative breast cancer (TNBC) risk with pathogenic variants (PV) in hereditary cancer predisposition genes Hall, M. J., Rosenthal, E., San Roman, S., Bernhisel, R., Kidd, J., Hughes, E., Slavin, T., Kurian, A. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737700114

• Integrating Clinical and Polygenic Factors to Predict Breast Cancer Risk in Women Undergoing Genetic Testing. JCO precision oncology Hughes, E., Tshiaba, P., Wagner, S., Judkins, T., Rosenthal, E., Roa, B., Gallagher, S., Meek, S., Dalton, K., Hedegard, W., Adami, C. A., Grear, D. F., Domchek, S. M., Garber, J., Lancaster, J. M., Weitzel, J. N., Kurian, A. W., Lanchbury, J. S., Gutin, A., Robson, M. E. 2021; 5

  Abstract

  Screening and prevention decisions for women at increased risk of developing breast cancer depend on genetic and clinical factors to estimate risk and select appropriate interventions. Integration of polygenic risk into clinical breast cancer risk estimators can improve discrimination. However, correlated genetic effects must be incorporated carefully to avoid overestimation of risk.A novel Fixed-Stratified method was developed that accounts for confounding when adding a new factor to an established risk model. A combined risk score (CRS) of an 86-single-nucleotide polymorphism polygenic risk score and the Tyrer-Cuzick v7.02 clinical risk estimator was generated with attenuation for confounding by family history. Calibration and discriminatory accuracy of the CRS were evaluated in two independent validation cohorts of women of European ancestry (N = 1,615 and N = 518). Discrimination for remaining lifetime risk was examined by age-adjusted logistic regression. Risk stratification with a 20% risk threshold was compared between CRS and Tyrer-Cuzick in an independent clinical cohort (N = 32,576).Simulation studies confirmed that the Fixed-Stratified method produced accurate risk estimation across patients with different family history. In both validation studies, CRS and Tyrer-Cuzick were significantly associated with breast cancer. In an analysis with both CRS and Tyrer-Cuzick as predictors of breast cancer, CRS added significant discrimination independent of that captured by Tyrer-Cuzick (P < 10-11 in validation 1; P < 10-7 in validation 2). In an independent cohort, 18% of women shifted breast cancer risk categories from their Tyrer-Cuzick-based risk compared with risk estimates by CRS.Integrating clinical and polygenic factors into a risk model offers more effective risk stratification and supports a personalized genomic approach to breast cancer screening and prevention.

  View details for DOI 10.1200/PO.20.00246

  View details for PubMedID 34036224

  View details for PubMedCentralID PMC8140787

• CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers. British journal of cancer Johnson, N. n., Maguire, S. n., Morra, A. n., Kapoor, P. M., Tomczyk, K. n., Jones, M. E., Schoemaker, M. J., Gilham, C. n., Bolla, M. K., Wang, Q. n., Dennis, J. n., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H. n., Antonenkova, N. N., Arndt, V. n., Aronson, K. J., Augustinsson, A. n., Baynes, C. n., Freeman, L. E., Beckmann, M. W., Benitez, J. n., Bermisheva, M. n., Blomqvist, C. n., Boeckx, B. n., Bogdanova, N. V., Bojesen, S. E., Brauch, H. n., Brenner, H. n., Burwinkel, B. n., Campa, D. n., Canzian, F. n., Castelao, J. E., Chanock, S. J., Chenevix-Trench, G. n., Clarke, C. L., Conroy, D. M., Couch, F. J., Cox, A. n., Cross, S. S., Czene, K. n., Dörk, T. n., Eliassen, A. H., Engel, C. n., Evans, D. G., Fasching, P. A., Figueroa, J. n., Floris, G. n., Flyger, H. n., Gago-Dominguez, M. n., Gapstur, S. M., García-Closas, M. n., Gaudet, M. M., Giles, G. G., Goldberg, M. S., González-Neira, A. n., Guénel, P. n., Hahnen, E. n., Haiman, C. A., Håkansson, N. n., Hall, P. n., Hamann, U. n., Harrington, P. A., Hart, S. N., Hooning, M. J., Hopper, J. L., Howell, A. n., Hunter, D. J., Jager, A. n., Jakubowska, A. n., John, E. M., Kaaks, R. n., Keeman, R. n., Khusnutdinova, E. n., Kitahara, C. M., Kosma, V. M., Koutros, S. n., Kraft, P. n., Kristensen, V. N., Kurian, A. W., Lambrechts, D. n., Le Marchand, L. n., Linet, M. n., Lubiński, J. n., Mannermaa, A. n., Manoukian, S. n., Margolin, S. n., Martens, J. W., Mavroudis, D. n., Mayes, R. n., Meindl, A. n., Milne, R. L., Neuhausen, S. L., Nevanlinna, H. n., Newman, W. G., Nielsen, S. F., Nordestgaard, B. G., Obi, N. n., Olshan, A. F., Olson, J. E., Olsson, H. n., Orban, E. n., Park-Simon, T. W., Peterlongo, P. n., Plaseska-Karanfilska, D. n., Pylkäs, K. n., Rennert, G. n., Rennert, H. S., Ruddy, K. J., Saloustros, E. n., Sandler, D. P., Sawyer, E. J., Schmutzler, R. K., Scott, C. n., Shu, X. O., Simard, J. n., Smichkoska, S. n., Sohn, C. n., Southey, M. C., Spinelli, J. J., Stone, J. n., Tamimi, R. M., Taylor, J. A., Tollenaar, R. A., Tomlinson, I. n., Troester, M. A., Truong, T. n., Vachon, C. M., van Veen, E. M., Wang, S. S., Weinberg, C. R., Wendt, C. n., Wildiers, H. n., Winqvist, R. n., Wolk, A. n., Zheng, W. n., Ziogas, A. n., Dunning, A. M., Pharoah, P. D., Easton, D. F., Howie, A. F., Peto, J. n., Dos-Santos-Silva, I. n., Swerdlow, A. J., Chang-Claude, J. n., Schmidt, M. K., Orr, N. n., Fletcher, O. n. 2021

  Abstract

  Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8).The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

  View details for DOI 10.1038/s41416-020-01185-w

  View details for PubMedID 33495599

• Development and Validation of a Simulation Model-Based Clinical Decision Tool: Identifying Patients Where 21-Gene Recurrence Score Testing May Change Decisions. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Jayasekera, J., Sparano, J. A., O'Neill, S., Chandler, Y., Isaacs, C., Kurian, A. W., Kushi, L., Schechter, C. B., Mandelblatt, J. 2021: JCO2100651

  Abstract

  There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor-positive, human epidermal growth factor receptor-2-negative (early-stage) breast cancer.We adapted an extant Cancer Intervention and Surveillance Modeling Network simulation model to estimate the 10-year risk of distant recurrence, breast cancer-specific mortality, other-cause mortality, and life-years gained with chemoendocrine versus endocrine therapy. We simulated outcomes for 1,512 unique patient subgroups based on all possible combinations of age, tumor size, grade, and comorbidity level; simulations were performed with and without 21-gene recurrence scores (RSs). Model inputs were derived from clinical trials, large US cohort studies, registry, and claims data. External validation was performed by comparing results to observed rates in two independent sources. We highlight results for one scenario where treatment choice may be uncertain.Chemoendocrine versus endocrine therapy in a 65-69-year-old woman with a small (≤ 2 cm), intermediate-grade tumor, and mild comorbidities provides a 1.3% absolute reduction in 10-year distant recurrence risk, with 0.23 life-years gained. With these tumor features, a woman like this will have a 28% probability of having an RS 16-20, 18% RS 21-25, and 11% RS 26+. If testing is done, and her RS is 16-20, chemoendocrine therapy reduces 10-year distant recurrence risk to 1%, with 0.20 life-years gained, a similar result as without testing. The absolute benefits would increase to 4.8%-5.5% if the RS was 26+. The model closely reproduced observed rates in both independent data sets.Our validated clinical decision tool is flexible, readily adaptable to include new therapies, and can support discussions about genomic testing and early breast cancer treatment.

  View details for DOI 10.1200/JCO.21.00651

  View details for PubMedID 34251881

• Influence of payer coverage and out-of-pocket costs on ordering of NGS panel tests for hereditary cancer in diverse settings. Journal of genetic counseling Lin, G. A., Trosman, J. R., Douglas, M. P., Weldon, C. B., Scheuner, M. T., Kurian, A., Phillips, K. A. 2021

  Abstract

  The landscape of payment for genetic testing has been changing, with an increase in the number of laboratories offering testing, larger panel offerings, and lower prices. To determine the influence of payer coverage and out-of-pocket costs on the ordering of NGS panel tests for hereditary cancer in diverse settings, we conducted semi-structured interviews with providers who conduct genetic counseling and order next-generation sequencing (NGS) panels purposefully recruited from 11 safety-net clinics and academic medical centers (AMCs) in California and North Carolina, states with diverse populations and divergent Medicaid expansion policies. Thematic analysis was done to identify themes related to the impact of reimbursement and out-of-pocket expenses on test ordering. Specific focus was put on differences between settings. Respondents from both safety-net clinics and AMCs reported that they are increasingly ordering panels instead of single-gene tests, and tests were ordered primarily from a few commercial laboratories. Surprisingly, safety-net clinics reported few barriers to testing related to cost, largely due to laboratory assistance with prior authorization requests and patient payment assistance programs that result in little to no patient out-of-pocket expenses. AMCs reported greater challenges navigating insurance issues, particularly prior authorization. Both groups cited non-coverage of genetic counseling as a major barrier to testing. Difficulty of access to cascade testing, particularly for family members that do not live in the United States, was also of concern. Long-term sustainability of laboratory payment assistance programs was a major concern; safety-net clinics were particularly concerned about access to testing without such programs. There were few differences between states. In conclusion, the use of laboratories with payment assistance programs reduces barriers to NGS panel testing among diverse populations. Such programs represent a major change to the financing and affordability of genetic testing. However, access to genetic counseling is a barrier and must be addressed to ensure equity in testing.

  View details for DOI 10.1002/jgc4.1459

  View details for PubMedID 34231930

• Impact of Low-Dose CT Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Su, C. C., Wu, J. T., Neal, J. W., Popat, R. A., Kurian, A. W., Backhus, L. M., Nagpal, S., Leung, A. N., Wakelee, H. A., Han, S. S. 2021

  Abstract

  Brain metastasis (BM) is one of the most common metastases from primary lung cancer (PLC). Recently, the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose computed tomography (LDCT) screening on LC mortality reduction. However, it remains unknown if early detection of PLC through LDCT may be potentially beneficial in reducing the risk of subsequent metastases. Our study aimed to investigate the impact of LDCT screening for PLC on the risk of developing BM after PLC diagnosis.We used NLST data to identify 1,502 participants who were diagnosed with PLC in 2002-2009 and have follow-up data for BM. Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection-i.e., LDCT screen-detected versus non-LDCT screen-detected. Subgroup analyses were conducted in early-stage PLC patients and those who underwent surgery for PLC.Of 1502 participants, 41.4% had PLC detected through LDCT-screening versus 58.6% detected through other methods, e.g., chest X-Ray or incidental detection. Patients whose PLC was detected with LDCT-screening had a significantly lower 3-year incidence of BM (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p=0.001), adjusting for PLC stage, histology, diagnosis age and smoking status. This significant reduction in BM risk among PLCs detected through LDCT-screening persisted in subgroups of early-stage PLC participants (HR 0.47, p=0.002) and those who underwent surgery (HR 0.37, p=0.001).Early detection of PLC using LDCT-screening is associated with lower risk of BM after PLC diagnosis based on a large population-based study.

  View details for DOI 10.1016/j.jtho.2021.05.010

  View details for PubMedID 34091050

• Greater Financial Toxicity Relates to Greater Distress and Worse Quality of Life Among Breast and Gynecologic Cancer Survivors. Psycho-oncology Benedict, C., Fisher, S., Schapira, L., Chao, S., Sackeyfio, S., Sullivan, T., Pollom, E., Berek, J. S., Kurian, A. W., Palesh, O. 2021

  Abstract

  Financial toxicity includes distress and burden from cancer-related costs. Women are more likely to experience worse cancer-related financial outcomes than men. This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL).A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire [PHQ-4]), and QOL (Functional Assessment of Cancer Therapy [FACT-G]). Chi-square, t-tests, and ANOVAs examined bivariate relationships. Two regression models tested associations between financial toxicity and distress and QOL, controlling for covariates. Financial toxicity subgroups were compared based on a validated grading system.Participants (N=273; 74% breast cancer) averaged 54.65 years (SD=12.08), were 3.42 years (SD=4.20) post-diagnosis, and 33% reported cancer-related change in employment status. Financial toxicity was "mild" overall (COST M=26.11, SD=11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). Worse financial toxicity related to younger age (p<.001), identifying as a non-Asian minority (p=.03) or Hispanic (p=.01), being single (p<.001), lower education (p=.004), lower income (p<.001), late-stage disease (p=.001), recurrent disease (p=.004), and active treatment (p<.001). In separate multivariable models, greater financial toxicity related to greater distress (β=-.45 p<.001) and worse QOL (β=.58, p<.001). Financial toxicity subgroups reported clinically significant differences in distress and QOL (p's<.05).Cancer-related financial burden is associated with pervasive negative effects and may impact subgroups differently. Future research should explore financial experiences across subgroups, aiming to better identify those at risk and build targeted interventions. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/pon.5763

  View details for PubMedID 34224603

• Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. American journal of human genetics Baxter, J. S., Johnson, N., Tomczyk, K., Gillespie, A., Maguire, S., Brough, R., Fachal, L., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Augustinsson, A., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N. V., Bojesen, S. E., Brenner, H., Brucker, S. Y., Cai, Q., Campa, D., Canzian, F., Castelao, J. E., Chan, T. L., Chang-Claude, J., Chanock, S. J., Chenevix-Trench, G., Choi, J. Y., Clarke, C. L., Colonna, S., Conroy, D. M., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dörk, T., Dossus, L., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Engel, C., Fasching, P. A., Figueroa, J., Flyger, H., Gago-Dominguez, M., Gao, C., García-Closas, M., García-Sáenz, J. A., Ghoussaini, M., Giles, G. G., Goldberg, M. S., González-Neira, A., Guénel, P., Gündert, M., Haeberle, L., Hahnen, E., Haiman, C. A., Hall, P., Hamann, U., Hartman, M., Hatse, S., Hauke, J., Hollestelle, A., Hoppe, R., Hopper, J. L., Hou, M. F., Ito, H., Iwasaki, M., Jager, A., Jakubowska, A., Janni, W., John, E. M., Joseph, V., Jung, A., Kaaks, R., Kang, D., Keeman, R., Khusnutdinova, E., Kim, S. W., Kosma, V. M., Kraft, P., Kristensen, V. N., Kubelka-Sabit, K., Kurian, A. W., Kwong, A., Lacey, J. V., Lambrechts, D., Larson, N. L., Larsson, S. C., Le Marchand, L., Lejbkowicz, F., Li, J., Long, J., Lophatananon, A., Lubiński, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Matsuo, K., Mavroudis, D., Mayes, R., Menon, U., Milne, R. L., Mohd Taib, N. A., Muir, K., Muranen, T. A., Murphy, R. A., Nevanlinna, H., O'Brien, K. M., Offit, K., Olson, J. E., Olsson, H., Park, S. K., Park-Simon, T. W., Patel, A. V., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Presneau, N., Pylkäs, K., Rack, B., Rennert, G., Romero, A., Ruebner, M., Rüdiger, T., Saloustros, E., Sandler, D. P., Sawyer, E. J., Schmidt, M. K., Schmutzler, R. K., Schneeweiss, A., Schoemaker, M. J., Shah, M., Shen, C. Y., Shu, X. O., Simard, J., Southey, M. C., Stone, J., Surowy, H., Swerdlow, A. J., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Teo, S. H., Teras, L. R., Terry, M. B., Toland, A. E., Tomlinson, I., Truong, T., Tseng, C. C., Untch, M., Vachon, C. M., van den Ouweland, A. M., Wang, S. S., Weinberg, C. R., Wendt, C., Winham, S. J., Winqvist, R., Wolk, A., Wu, A. H., Yamaji, T., Zheng, W., Ziogas, A., Pharoah, P. D., Dunning, A. M., Easton, D. F., Pettitt, S. J., Lord, C. J., Haider, S., Orr, N., Fletcher, O. 2021

  Abstract

  A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).

  View details for DOI 10.1016/j.ajhg.2021.05.013

  View details for PubMedID 34146516

• Receipt of guideline-concordant care among young adult women with breast cancer. Cancer White, D. P., Kurian, A. W., Stevens, J. L., Liu, B., Brest, A. E., Petkov, V. I. 2021

  Abstract

  Little is known about the real-world care of young adult (YA) females (aged 20-39 years) with breast cancer. This study describes factors associated with the receipt of guideline-concordant care (GCC) among YAs.The authors identified 1259 YA women with invasive breast cancer diagnosed in 2013 in the National Cancer Institute's Patterns of Care study. Hospital records were re-abstracted, and treatment was verified. Using the National Comprehensive Cancer Network's 2013 breast cancer guidelines, the authors assessed the receipt of GCC by cancer subtype among a subset of YAs (n = 952). Associations between sociodemographic and clinical factors and GCC receipt were examined.Most YAs were 35 to 39 years old (51.2%) and partnered (56.4%); half had hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. GCC was found for 81.7% of YAs. Relationships between sociodemographic and clinical factors and GCC receipt differed by subtype. Stage was the only significant predictor of GCC receipt for all subtypes (stage II vs III: odds ratio [OR] for HR+/HER2+, 0.20; 95% confidence interval [CI], 0.08-0.50; OR for HR-/HER2+, 0.13; 95% CI, 0.07-0.25; OR for HR-/HER2-, 3.86; 95% CI, 1.55-9.62; OR for HR+/HER2-, 2.81; 95% CI, 1.63-5.80).GCC is high among YAs with breast cancer. The effects of sociodemographic factors and treatment facility size on GCC differ by subtype. Consistent with recommendations, tumor biology, not age, is associated with GCC for all subtypes. Future studies should assess the effect of GCC on survival among YAs.

  View details for DOI 10.1002/cncr.33652

  View details for PubMedID 34062616

• Treatment and Monitoring Variability in US Metastatic Breast Cancer Care. JCO clinical cancer informatics Caswell-Jin, J. L., Callahan, A., Purington, N., Han, S. S., Itakura, H., John, E. M., Blayney, D. W., Sledge, G. W., Shah, N. H., Kurian, A. W. 2021; 5: 600-614

  Abstract

  Treatment and monitoring options for patients with metastatic breast cancer (MBC) are increasing, but little is known about variability in care. We sought to improve understanding of MBC care and its correlates by analyzing real-world claims data using a search engine with a novel query language to enable temporal electronic phenotyping.Using the Advanced Cohort Engine, we identified 6,180 women who met criteria for having estrogen receptor-positive, human epidermal growth factor receptor 2-negative MBC from IBM MarketScan US insurance claims (2007-2014). We characterized treatment, monitoring, and hospice usage, along with clinical and nonclinical factors affecting care.We observed wide variability in treatment modality and monitoring across patients and geography. Most women received first-recorded therapy with endocrine (67%) versus chemotherapy, underwent more computed tomography (CT) (76%) than positron emission tomography-CT, and were monitored using tumor markers (58%). Nearly half (46%) met criteria for aggressive disease, which were associated with receiving chemotherapy first, monitoring primarily with CT, and more frequent imaging. Older age was associated with endocrine therapy first, less frequent imaging, and less use of tumor markers. After controlling for clinical factors, care strategies varied significantly by nonclinical factors (median regional income with first-recorded therapy and imaging type, geographic region with these and with imaging frequency and use of tumor markers; P < .0001).Variability in US MBC care is explained by patient and disease factors and by nonclinical factors such as geographic region, suggesting that treatment decisions are influenced by local practice patterns and/or resources. A search engine designed to express complex electronic phenotypes from longitudinal patient records enables the identification of variability in patient care, helping to define disparities and areas for improvement.

  View details for DOI 10.1200/CCI.21.00031

  View details for PubMedID 34043432

• Comprehensive Breast Cancer Risk Assessment for CHEK2 and ATM Pathogenic Variant Carriers Incorporating a Polygenic Risk Score and the Tyrer-Cuzick Model JCO Precision Oncology Gallagher, S., Hughes, E., Kurian, A. W., Domchek, S. M., Garber, J., Probst, B., Morris, B., Tshiaba, P., Meek, S., Rosenthal, E., Roa, B., Slavin, T. P., Wagner, S., Weitzel, J., Gutin, A., Lanchbury, J. S., Robson, M. 2021; 5: 1073-81

  View details for DOI 10.1200/PO.20.00484

• Performance of the IBIS/Tyrer-Cuzick model of breast cancer risk by race and ethnicity in the Women's Health Initiative. Cancer Kurian, A. W., Hughes, E., Simmons, T., Bernhisel, R., Probst, B., Meek, S., Caswell-Jin, J. L., John, E. M., Lanchbury, J. S., Slavin, T. P., Wagner, S., Gutin, A., Rohan, T. E., Shadyab, A. H., Manson, J. E., Lane, D., Chlebowski, R. T., Stefanick, M. L. 2021

  Abstract

  The IBIS/Tyrer-Cuzick model is used clinically to guide breast cancer screening and prevention, but was developed primarily in non-Hispanic White women. Little is known about its long-term performance in a racially/ethnically diverse population.The Women's Health Initiative study enrolled postmenopausal women from 1993-1998. Women were included who were aged <80 years at enrollment with no prior breast cancer or mastectomy and with data required for IBIS/Tyrer-Cuzick calculation (weight; height; ages at menarche, first birth, and menopause; menopausal hormone therapy use; and family history of breast or ovarian cancer). Calibration was assessed by the ratio of observed breast cancer cases to the number expected by the IBIS/Tyrer-Cuzick model (O/E; calculated as the sum of cumulative hazards). Differential discrimination was tested for by self-reported race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian or Pacific Islander, and American Indian or Alaskan Native) using Cox regression. Exploratory analyses, including simulation of a protective single-nucleotide polymorphism (SNP), rs140068132 at 6q25, were performed.During follow-up (median 18.9 years, maximum 23.4 years), 6783 breast cancer cases occurred among 90,967 women. IBIS/Tyrer-Cuzick was well calibrated overall (O/E ratio = 0.95; 95% CI, 0.93-0.97) and in most racial/ethnic groups, but overestimated risk for Hispanic women (O/E ratio = 0.75; 95% CI, 0.62-0.90). Discrimination did not differ by race/ethnicity. Exploratory simulation of the protective SNP suggested improved IBIS/Tyrer-Cuzick calibration for Hispanic women (O/E ratio = 0.80; 95% CI, 0.66-0.96).The IBIS/Tyrer-Cuzick model is well calibrated for several racial/ethnic groups over 2 decades of follow-up. Studies that incorporate genetic and other risk factors, particularly among Hispanic women, are essential to improve breast cancer-risk prediction.

  View details for DOI 10.1002/cncr.33767

  View details for PubMedID 34228814

• Weight is more informative than body mass index for predicting post-menopausal breast cancer risk: Prospective Family Study Cohort (ProF-SC). Cancer prevention research (Philadelphia, Pa.) Ye, Z., Li, S., Dite, G. S., Nguyen, T. L., MacInnis, R. J., Andrulis, I. L., Buys, S. S., Daly, M. B., John, E. M., Kurian, A. W., Genkinger, J. M., Chung, W. K., Phillips, K. A., Thorne, H., Winship, I. M., Milne, R. L., Dugué, P. A., Southey, M. C., Giles, G. G., Terry, M. B., Hopper, J. L. 2021

  Abstract

  We considered whether weight is more informative than body mass index = weight/height2 (BMI) when predicting breast cancer risk for post-menopausal women, and if the weight association differs by underlying familial risk. We studied 6,761 women post-menopausal at baseline with a wide range of familial risk from 2,364 families in the Prospective Family Study Cohort (ProF-SC). Participants were followed for on average 11.45 years and there were 416 incident breast cancers. We used Cox regression to estimate risk associations with log-transformed weight and BMI after adjusting for underlying familial risk. We compared model fits using the Akaike Information Criterion (AIC) and nested models using the likelihood ratio test. The AIC for the weight-only model was 6.22 units lower than for the BMI-only model, and the log risk gradient was 23% greater. Adding BMI or height to weight did not improve fit (ΔAIC=0.90 and 0.83, respectively; both P=0.3). Conversely, adding weight to BMI or height gave better fits (ΔAIC=5.32 and 11.64; P=0.007 and 0.0002, respectively). Adding height improved only the BMI model (ΔAIC=5.47; P=0.006). There was no evidence that the BMI or weight associations differed by underlying familial risk (P>0.2). Weight is more informative than BMI for predicting breast cancer risk, consistent with non-adipose as well as adipose tissue being etiologically relevant. The independent but multiplicative associations of weight and familial risk suggest that, in terms of absolute breast cancer risk, the association with weight is more important the greater a woman's underlying familial risk.

  View details for DOI 10.1158/1940-6207.CAPR-21-0164

  View details for PubMedID 34965921

• Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British journal of cancer Park, H. A., Neumeyer, S., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Augustinsson, A., Baten, A., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N. V., Bojesen, S. E., Brauch, H., Brenner, H., Brucker, S. Y., Burwinkel, B., Campa, D., Canzian, F., Castelao, J. E., Chanock, S. J., Chenevix-Trench, G., Clarke, C. L., Conroy, D. M., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dörk, T., Dos-Santos-Silva, I., Dwek, M., Eccles, D. M., Eliassen, A. H., Engel, C., Eriksson, M., Evans, D. G., Fasching, P. A., Flyger, H., Fritschi, L., García-Closas, M., García-Sáenz, J. A., Gaudet, M. M., Giles, G. G., Glendon, G., Goldberg, M. S., Goldgar, D. E., González-Neira, A., Grip, M., Guénel, P., Hahnen, E., Haiman, C. A., Håkansson, N., Hall, P., Hamann, U., Han, S., Harkness, E. F., Hart, S. N., He, W., Heemskerk-Gerritsen, B. A., Hopper, J. L., Hunter, D. J., Jager, A., Jakubowska, A., John, E. M., Jung, A., Kaaks, R., Kapoor, P. M., Keeman, R., Khusnutdinova, E., Kitahara, C. M., Koppert, L. B., Koutros, S., Kristensen, V. N., Kurian, A. W., Lacey, J., Lambrechts, D., Le Marchand, L., Lo, W. Y., Lubiński, J., Mannermaa, A., Manoochehri, M., Margolin, S., Martinez, M. E., Mavroudis, D., Meindl, A., Menon, U., Milne, R. L., Muranen, T. A., Nevanlinna, H., Newman, W. G., Nordestgaard, B. G., Offit, K., Olshan, A. F., Olsson, H., Park-Simon, T. W., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Presneau, N., Radice, P., Rennert, G., Rennert, H. S., Romero, A., Saloustros, E., Sawyer, E. J., Schmidt, M. K., Schmutzler, R. K., Schoemaker, M. J., Schwentner, L., Scott, C., Shah, M., Shu, X. O., Simard, J., Smeets, A., Southey, M. C., Spinelli, J. J., Stevens, V., Swerdlow, A. J., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Terry, M. B., Tomlinson, I., Troester, M. A., Truong, T., Vachon, C. M., van Veen, E. M., Vijai, J., Wang, S., Wendt, C., Winqvist, R., Wolk, A., Ziogas, A., Dunning, A. M., Pharoah, P. D., Easton, D. F., Zheng, W., Kraft, P., Chang-Claude, J. 2021

  Abstract

  Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

  View details for DOI 10.1038/s41416-021-01432-8

  View details for PubMedID 34341517

• Simulation modeling of breast cancer endocrine therapy duration by patient and tumor characteristics. Cancer medicine Chandler, Y., Schechter, C., Jayasekera, J., Isaacs, C., Kurian, A. W., Cadham, C., Mandelblatt, J. 2021

  Abstract

  Extending endocrine therapy from 5 to 10 years is recommended for women with invasive estrogen receptor (ER)-positive breast cancers. We evaluated the benefits and harms of the five additional years of therapy.An established Cancer Intervention and Surveillance Network (CISNET) model used a lifetime horizon with national and clinical trial data on treatment efficacy and adverse events and other-cause mortality among multiple birth cohorts of U.S. women ages 25-79 newly diagnosed with ER+, non-metastatic breast cancer. We assumed 100% use of therapy. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer mortality. Results were discounted at 3%. Sensitivity analyses tested a 15-year time horizon and alternative assumptions.Extending tamoxifen therapy duration among women ages 25-49 reduced the lifetime probability of breast cancer death from 11.9% to 9.3% (absolute difference 2.6%). This translates to a gain of 0.77 LYs (281 days)/woman (undiscounted). Adverse events reduce this gain to 0.44 QALYs and after discounting, gains are 0.20 QALYs (73 days)/woman. Extended aromatase inhibitor therapy in women 50-79 had small absolute benefits and gains were offset by adverse events (loss of 0.06 discounted QALYs). There were greater gains with extended endocrine therapy for women with node-positive versus negative cancers, but only women ages 25-49 and 50-59 had a net QALY gain. All gains were reduced with less than 100% treatment completion.The extension of endocrine therapy from 5 to 10 years modestly improved lifetime breast cancer outcomes, but in some women, treatment-related adverse events may outweigh benefits.

  View details for DOI 10.1002/cam4.4084

  View details for PubMedID 34918484

• Racial/ethnic differences in cancer diagnosed after metastasis: absolute burden and deaths potentially avoidable through earlier detection. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Clarke, C. A., Patel, A. V., Kurian, A. W., Hubbell, E., Gomez, S. L. 2021

  Abstract

  Racial/ethnic disparities in cancer mortality are well-described and are partly attributable to later stage of diagnosis. It is unclear to what extent reductions in the incidence of late-stage cancer could narrow these relative and absolute disparities.We obtained stage- and cancer-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for persons aged 50 to 79 years between 2006 and 2015. For eight hypothetical cohorts of 100,000 persons defined by race/ethnicity and sex, we estimated cancer-related deaths if cancers diagnosed at stage IV were detected earlier, by assigning them outcomes of earlier stages.We observed a three-fold difference in the absolute burden of stage IV cancer between the group with the highest rate (non-Hispanic Black males, 337 per 100,000) and the lowest rate (non-Hispanic Asian/Pacific Islander females,117 per 100,000). Assuming all stage IV cancers were diagnosed at stage III, 32-80 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 13-14%. Assuming one-third of metastatic cancers were diagnosed at each earlier stage (I, II, and III), 52-126 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 21-23%.Across population subgroups, non-Hispanic Black males have the highest burden of stage IV cancer and would have the most deaths averted from improved detection of cancer before metastasis.Detecting cancer before metastasis could meaningfully reduce deaths in all populations, but especially in non-Hispanic Black populations.

  View details for DOI 10.1158/1055-9965.EPI-21-0823

  View details for PubMedID 34810206

• Association of Family Cancer History With Pathogenic Variants in Specific Breast Cancer Susceptibility Genes. JCO precision oncology Kurian, A. W., Abrahamse, P., Ward, K. C., Hamilton, A. S., Deapen, D., Berek, J. S., Hoang, L., Yussuf, A., Dolinsky, J., Brown, K., Slavin, T., Hofer, T. P., Katz, S. J. 2021; 5

  Abstract

  Family cancer history is an important component of genetic testing guidelines that estimate which patients with breast cancer are most likely to carry a germline pathogenic variant (PV). However, we do not know whether more extensive family history is differentially associated with PVs in specific genes.All women diagnosed with breast cancer in 2013-2017 and reported to statewide SEER registries of Georgia and California were linked to clinical genetic testing results and family history from two laboratories. Family history was defined as strong (suggestive of PVs in high-penetrance genes such as BRCA1/2 or TP53, including male breast, ovarian, pancreatic, sarcoma, or multiple female breast cancers), moderate (any other cancer history), or none. Among established breast cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53), we evaluated PV prevalence according to family history extent and breast cancer subtype. We used a multivariable model to test for interaction between affected gene and family history extent for ATM, BRCA1/2, CHEK2, and PALB2.A total of 34,865 women linked to genetic results. Higher PV prevalence with increasing family history extent (P < .001) was observed only with BRCA1 (3.04% with none, 3.22% with moderate, and 4.06% with strong history) and in triple-negative breast cancer with PALB2 (0.75% with none, 2.23% with moderate, and 2.63% with strong history). In a multivariable model adjusted for age and subtype, there was no interaction between family history extent and PV prevalence for any gene except PALB2 (P = .037).Extent of family cancer history is not differentially associated with PVs across established breast cancer susceptibility genes and cannot be used to personalize genes selected for testing.

  View details for DOI 10.1200/PO.21.00261

  View details for PubMedID 34977446

  View details for PubMedCentralID PMC8710333

• Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States. JAMA oncology Domchek, S. M., Yao, S., Chen, F., Hu, C., Hart, S. N., Goldgar, D. E., Nathanson, K. L., Ambrosone, C. B., Haiman, C. A., Couch, F. J., Polley, E. C., Palmer, J. R. 2021

  Abstract

  The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.Prevalence of germline PVs in 12 established breast cancer susceptibility genes.Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor-negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.

  View details for DOI 10.1001/jamaoncol.2021.1492

  View details for PubMedID 34042955

• Polygenic risk scores for prediction of breast cancer risk in Asian populations. Genetics in medicine : official journal of the American College of Medical Genetics Ho, W. K., Tai, M. C., Dennis, J., Shu, X., Li, J., Ho, P. J., Millwood, I. Y., Lin, K., Jee, Y. H., Lee, S. H., Mavaddat, N., Bolla, M. K., Wang, Q., Michailidou, K., Long, J., Wijaya, E. A., Hassan, T., Rahmat, K., Tan, V. K., Tan, B. K., Tan, S. M., Tan, E. Y., Lim, S. H., Gao, Y. T., Zheng, Y., Kang, D., Choi, J. Y., Han, W., Lee, H. B., Kubo, M., Okada, Y., Namba, S., Park, S. K., Kim, S. W., Shen, C. Y., Wu, P. E., Park, B., Muir, K. R., Lophatananon, A., Wu, A. H., Tseng, C. C., Matsuo, K., Ito, H., Kwong, A., Chan, T. L., John, E. M., Kurian, A. W., Iwasaki, M., Yamaji, T., Kweon, S. S., Aronson, K. J., Murphy, R. A., Koh, W. P., Khor, C. C., Yuan, J. M., Dorajoo, R., Walters, R. G., Chen, Z., Li, L., Lv, J., Jung, K. J., Kraft, P., Pharoah, P. D., Dunning, A. M., Simard, J., Shu, X. O., Yip, C. H., Taib, N. A., Antoniou, A. C., Zheng, W., Hartman, M., Easton, D. F., Teo, S. H. 2021

  Abstract

  Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

  View details for DOI 10.1016/j.gim.2021.11.008

  View details for PubMedID 34906514

• Genetic insights into biological mechanisms governing human ovarian ageing. Nature Ruth, K. S., Day, F. R., Hussain, J., Martínez-Marchal, A., Aiken, C. E., Azad, A., Thompson, D. J., Knoblochova, L., Abe, H., Tarry-Adkins, J. L., Gonzalez, J. M., Fontanillas, P., Claringbould, A., Bakker, O. B., Sulem, P., Walters, R. G., Terao, C., Turon, S., Horikoshi, M., Lin, K., Onland-Moret, N. C., Sankar, A., Hertz, E. P., Timshel, P. N., Shukla, V., Borup, R., Olsen, K. W., Aguilera, P., Ferrer-Roda, M., Huang, Y., Stankovic, S., Timmers, P. R., Ahearn, T. U., Alizadeh, B. Z., Naderi, E., Andrulis, I. L., Arnold, A. M., Aronson, K. J., Augustinsson, A., Bandinelli, S., Barbieri, C. M., Beaumont, R. N., Becher, H., Beckmann, M. W., Benonisdottir, S., Bergmann, S., Bochud, M., Boerwinkle, E., Bojesen, S. E., Bolla, M. K., Boomsma, D. I., Bowker, N., Brody, J. A., Broer, L., Buring, J. E., Campbell, A., Campbell, H., Castelao, J. E., Catamo, E., Chanock, S. J., Chenevix-Trench, G., Ciullo, M., Corre, T., Couch, F. J., Cox, A., Crisponi, L., Cross, S. S., Cucca, F., Czene, K., Smith, G. D., de Geus, E. J., de Mutsert, R., De Vivo, I., Demerath, E. W., Dennis, J., Dunning, A. M., Dwek, M., Eriksson, M., Esko, T., Fasching, P. A., Faul, J. D., Ferrucci, L., Franceschini, N., Frayling, T. M., Gago-Dominguez, M., Mezzavilla, M., García-Closas, M., Gieger, C., Giles, G. G., Grallert, H., Gudbjartsson, D. F., Gudnason, V., Guénel, P., Haiman, C. A., Håkansson, N., Hall, P., Hayward, C., He, C., He, W., Heiss, G., Høffding, M. K., Hopper, J. L., Hottenga, J. J., Hu, F., Hunter, D., Ikram, M. A., Jackson, R. D., Joaquim, M. D., John, E. M., Joshi, P. K., Karasik, D., Kardia, S. L., Kartsonaki, C., Karlsson, R., Kitahara, C. M., Kolcic, I., Kooperberg, C., Kraft, P., Kurian, A. W., Kutalik, Z., La Bianca, M., LaChance, G., Langenberg, C., Launer, L. J., Laven, J. S., Lawlor, D. A., Le Marchand, L., Li, J., Lindblom, A., Lindstrom, S., Lindstrom, T., Linet, M., Liu, Y., Liu, S., Luan, J., Mägi, R., Magnusson, P. K., Mangino, M., Mannermaa, A., Marco, B., Marten, J., Martin, N. G., Mbarek, H., McKnight, B., Medland, S. E., Meisinger, C., Meitinger, T., Menni, C., Metspalu, A., Milani, L., Milne, R. L., Montgomery, G. W., Mook-Kanamori, D. O., Mulas, A., Mulligan, A. M., Murray, A., Nalls, M. A., Newman, A., Noordam, R., Nutile, T., Nyholt, D. R., Olshan, A. F., Olsson, H., Painter, J. N., Patel, A. V., Pedersen, N. L., Perjakova, N., Peters, A., Peters, U., Pharoah, P. D., Polasek, O., Porcu, E., Psaty, B. M., Rahman, I., Rennert, G., Rennert, H. S., Ridker, P. M., Ring, S. M., Robino, A., Rose, L. M., Rosendaal, F. R., Rossouw, J., Rudan, I., Rueedi, R., Ruggiero, D., Sala, C. F., Saloustros, E., Sandler, D. P., Sanna, S., Sawyer, E. J., Sarnowski, C., Schlessinger, D., Schmidt, M. K., Schoemaker, M. J., Schraut, K. E., Scott, C., Shekari, S., Shrikhande, A., Smith, A. V., Smith, B. H., Smith, J. A., Sorice, R., Southey, M. C., Spector, T. D., Spinelli, J. J., Stampfer, M., Stöckl, D., van Meurs, J. B., Strauch, K., Styrkarsdottir, U., Swerdlow, A. J., Tanaka, T., Teras, L. R., Teumer, A., Þorsteinsdottir, U., Timpson, N. J., Toniolo, D., Traglia, M., Troester, M. A., Truong, T., Tyrrell, J., Uitterlinden, A. G., Ulivi, S., Vachon, C. M., Vitart, V., Völker, U., Vollenweider, P., Völzke, H., Wang, Q., Wareham, N. J., Weinberg, C. R., Weir, D. R., Wilcox, A. N., van Dijk, K. W., Willemsen, G., Wilson, J. F., Wolffenbuttel, B. H., Wolk, A., Wood, A. R., Zhao, W., Zygmunt, M., Chen, Z., Li, L., Franke, L., Burgess, S., Deelen, P., Pers, T. H., Grøndahl, M. L., Andersen, C. Y., Pujol, A., Lopez-Contreras, A. J., Daniel, J. A., Stefansson, K., Chang-Claude, J., van der Schouw, Y. T., Lunetta, K. L., Chasman, D. I., Easton, D. F., Visser, J. A., Ozanne, S. E., Namekawa, S. H., Solc, P., Murabito, J. M., Ong, K. K., Hoffmann, E. R., Murray, A., Roig, I., Perry, J. R. 2021

  Abstract

  Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.

  View details for DOI 10.1038/s41586-021-03779-7

  View details for PubMedID 34349265

• Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Yadav, S., Hu, C., Nathanson, K. L., Weitzel, J. N., Goldgar, D. E., Kraft, P., Gnanaolivu, R. D., Na, J., Huang, H., Boddicker, N. J., Larson, N., Gao, C., Yao, S., Weinberg, C., Vachon, C. M., Trentham-Dietz, A., Taylor, J. A., Sandler, D. R., Patel, A., Palmer, J. R., Olson, J. E., Neuhausen, S., Martinez, E., Lindstrom, S., Lacey, J. V., Kurian, A. W., John, E. M., Haiman, C., Bernstein, L., Auer, P. W., Anton-Culver, H., Ambrosone, C. B., Karam, R., Chao, E., Yussuf, A., Pesaran, T., Dolinsky, J. S., Hart, S. N., LaDuca, H., Polley, E. C., Domchek, S. M., Couch, F. J. 2021: JCO2100640

  Abstract

  To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.

  View details for DOI 10.1200/JCO.21.00640

  View details for PubMedID 34672684

• Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis. Scientific reports Escala-Garcia, M., Canisius, S., Keeman, R., Beesley, J., Anton-Culver, H., Arndt, V., Augustinsson, A., Becher, H., Beckmann, M. W., Behrens, S., Bermisheva, M., Bojesen, S. E., Bolla, M. K., Brenner, H., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Couch, F. J., Czene, K., Daly, M. B., Dennis, J., Devilee, P., Dörk, T., Dunning, A. M., Easton, D. F., Ekici, A. B., Eliassen, A. H., Fasching, P. A., Flyger, H., Gago-Dominguez, M., García-Closas, M., García-Sáenz, J. A., Geisler, J., Giles, G. G., Grip, M., Gündert, M., Hahnen, E., Haiman, C. A., Håkansson, N., Hall, P., Hamann, U., Hartikainen, J. M., Heemskerk-Gerritsen, B. A., Hollestelle, A., Hoppe, R., Hopper, J. L., Hunter, D. J., Jacot, W., Jakubowska, A., John, E. M., Jung, A. Y., Kaaks, R., Khusnutdinova, E., Koppert, L. B., Kraft, P., Kristensen, V. N., Kurian, A. W., Lambrechts, D., Le Marchand, L., Lindblom, A., Luben, R. N., Lubiński, J., Mannermaa, A., Manoochehri, M., Margolin, S., Mavroudis, D., Muranen, T. A., Nevanlinna, H., Olshan, A. F., Olsson, H., Park-Simon, T. W., Patel, A. V., Peterlongo, P., Pharoah, P. D., Punie, K., Radice, P., Rennert, G., Rennert, H. S., Romero, A., Roylance, R., Rüdiger, T., Ruebner, M., Saloustros, E., Sawyer, E. J., Schmutzler, R. K., Schoemaker, M. J., Scott, C., Southey, M. C., Surowy, H., Swerdlow, A. J., Tamimi, R. M., Teras, L. R., Thomas, E., Tomlinson, I., Troester, M. A., Vachon, C. M., Wang, Q., Winqvist, R., Wolk, A., Ziogas, A., Michailidou, K., Chenevix-Trench, G., Bachelot, T., Schmidt, M. K. 2021; 11 (1): 19787

  Abstract

  Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10-8 and 4.42 × 10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

  View details for DOI 10.1038/s41598-021-99409-3

  View details for PubMedID 34611289

• Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. Breast cancer research : BCR Morra, A., Escala-Garcia, M., Beesley, J., Keeman, R., Canisius, S., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Arndt, V., Auer, P. L., Augustinsson, A., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Bojesen, S. E., Bolla, M. K., Brenner, H., Brüning, T., Buys, S. S., Caan, B., Campa, D., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Cheng, T. D., Clarke, C. L., Colonna, S. V., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Dennis, J., Dörk, T., Dossus, L., Dunning, A. M., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Eriksson, M., Evans, D. G., Fasching, P. A., Flyger, H., Fritschi, L., Gago-Dominguez, M., García-Sáenz, J. A., Giles, G. G., Grip, M., Guénel, P., Gündert, M., Hahnen, E., Haiman, C. A., Håkansson, N., Hall, P., Hamann, U., Hart, S. N., Hartikainen, J. M., Hartmann, A., He, W., Hooning, M. J., Hoppe, R., Hopper, J. L., Howell, A., Hunter, D. J., Jager, A., Jakubowska, A., Janni, W., John, E. M., Jung, A. Y., Kaaks, R., Keupers, M., Kitahara, C. M., Koutros, S., Kraft, P., Kristensen, V. N., Kurian, A. W., Lacey, J. V., Lambrechts, D., Le Marchand, L., Lindblom, A., Linet, M., Luben, R. N., Lubiński, J., Lush, M., Mannermaa, A., Manoochehri, M., Margolin, S., Martens, J. W., Martinez, M. E., Mavroudis, D., Michailidou, K., Milne, R. L., Mulligan, A. M., Muranen, T. A., Nevanlinna, H., Newman, W. G., Nielsen, S. F., Nordestgaard, B. G., Olshan, A. F., Olsson, H., Orr, N., Park-Simon, T. W., Patel, A. V., Peissel, B., Peterlongo, P., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Rack, B., Rennert, G., Rennert, H. S., Rhenius, V., Romero, A., Roylance, R., Ruebner, M., Saloustros, E., Sawyer, E. J., Schmutzler, R. K., Schneeweiss, A., Scott, C., Shah, M., Smichkoska, S., Southey, M. C., Stone, J., Surowy, H., Swerdlow, A. J., Tamimi, R. M., Tapper, W. J., Teras, L. R., Terry, M. B., Tollenaar, R. A., Tomlinson, I., Troester, M. A., Truong, T., Vachon, C. M., Wang, Q., Hurson, A. N., Winqvist, R., Wolk, A., Ziogas, A., Brauch, H., García-Closas, M., Pharoah, P. D., Easton, D. F., Chenevix-Trench, G., Schmidt, M. K. 2021; 23 (1): 86

  Abstract

  Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

  View details for DOI 10.1186/s13058-021-01450-7

  View details for PubMedID 34407845

• Recreational Physical Activity and Outcomes After Breast Cancer in Women at High Familial Risk. JNCI cancer spectrum Kehm, R. D., MacInnis, R. J., John, E. M., Liao, Y., Kurian, A. W., Genkinger, J. M., Knight, J. A., Colonna, S. V., Chung, W. K., Milne, R., Zeinomar, N., Dite, G. S., Southey, M. C., Giles, G. G., McLachlan, S. A., Whitaker, K. D., Friedlander, M. L., Weideman, P. C., Glendon, G., Nesci, S., Phillips, K. A., Andrulis, I. L., Buys, S. S., Daly, M. B., Hopper, J. L., Terry, M. B. 2021; 5 (6): pkab090

  Abstract

  Recreational physical activity (RPA) is associated with improved survival after breast cancer (BC) in average-risk women, but evidence is limited for women who are at increased familial risk because of a BC family history or BRCA1 and BRCA2 pathogenic variants (BRCA1/2 PVs).We estimated associations of RPA (self-reported average hours per week within 3 years of BC diagnosis) with all-cause mortality and second BC events (recurrence or new primary) after first invasive BC in women in the Prospective Family Study Cohort (n = 4610, diagnosed 1993-2011, aged 22-79 years at diagnosis). We fitted Cox proportional hazards regression models adjusted for age at diagnosis, demographics, and lifestyle factors. We tested for multiplicative interactions (Wald test statistic for cross-product terms) and additive interactions (relative excess risk due to interaction) by age at diagnosis, body mass index, estrogen receptor status, stage at diagnosis, BRCA1/2 PVs, and familial risk score estimated from multigenerational pedigree data. Statistical tests were 2-sided.We observed 1212 deaths and 473 second BC events over a median follow-up from study enrollment of 11.0 and 10.5 years, respectively. After adjusting for covariates, RPA (any vs none) was associated with lower all-cause mortality of 16.1% (95% confidence interval [CI] = 2.4% to 27.9%) overall, 11.8% (95% CI = -3.6% to 24.9%) in women without BRCA1/2 PVs, and 47.5% (95% CI = 17.4% to 66.6%) in women with BRCA1/2 PVs (RPA*BRCA1/2 multiplicative interaction P = .005; relative excess risk due to interaction = 0.87, 95% CI = 0.01 to 1.74). RPA was not associated with risk of second BC events.Findings support that RPA is associated with lower all-cause mortality in women with BC, particularly in women with BRCA1/2 PVs.

  View details for DOI 10.1093/jncics/pkab090

  View details for PubMedID 34950851

  View details for PubMedCentralID PMC8692829

• Impact of the COVID-19 Pandemic on Breast Cancer Mortality in the US: Estimates From Collaborative Simulation Modeling. Journal of the National Cancer Institute Alagoz, O., Lowry, K. P., Kurian, A. W., Mandelblatt, J. S., Ergun, M. A., Huang, H., Lee, S. J., Schechter, C. B., Tosteson, A. N., Miglioretti, D. L., Trentham-Dietz, A., Nyante, S. J., Kerlikowske, K., Sprague, B. L., Stout, N. K. 2021

  Abstract

  The coronavirus disease 2019 (COVID-19) pandemic has disrupted breast cancer control through short-term declines in screening and delays in diagnosis and treatments. We projected the impact of COVID-19 on future breast cancer mortality between 2020 and 2030.Three established Cancer Intervention and Surveillance Modeling Network breast cancer models modeled reductions in mammography screening use, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first 6 months of the pandemic with return to prepandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact.By 2030, the models project 950 (model range = 860-1297) cumulative excess breast cancer deaths related to reduced screening, 1314 (model range = 266-1325) associated with delayed diagnosis of symptomatic cases, and 151 (model range = 146-207) associated with reduced chemotherapy use in women with hormone positive, early-stage cancer. Jointly, 2487 (model range = 1713-2575) excess breast cancer deaths were estimated, representing a 0.52% (model range = 0.36%-0.56%) cumulative increase over breast cancer deaths expected by 2030 in the absence of the pandemic's disruptions. Sensitivity analyses indicated that the breast cancer mortality impact would be approximately double if the modeled pandemic effects on screening, symptomatic diagnosis, and chemotherapy extended for 12 months.Initial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. Continued efforts to ensure prompt return to screening and minimize delays in evaluation of symptomatic women can largely mitigate the effects of the initial pandemic-associated disruptions.

  View details for DOI 10.1093/jnci/djab097

  View details for PubMedID 34258611

• Limited English Proficiency and Disparities in Health Care Engagement Among Patients With Breast Cancer. JCO oncology practice Roy, M. n., Purington, N. n., Liu, M. n., Blayney, D. W., Kurian, A. W., Schapira, L. n. 2021: OP2001093

  Abstract

  Race and ethnicity have been shown to affect quality of cancer care, and patients with low English proficiency (LEP) have increased risk for serious adverse events. We sought to assess the impact of primary language on health care engagement as indicated by clinical trial screening and engagement, use of genetic counseling, and communication via an electronic patient portal.Clinical and demographic data on patients with breast cancer diagnosed and treated from 2013 to 2018 within the Stanford University Health Care system were compiled via linkage of electronic health records, an internal clinical trial database, and the California Cancer Registry. Logistic and linear regression models were used to evaluate for association of clinical trial engagement and patient portal message rates with primary language group.Patients with LEP had significantly lower rates of clinical trial engagement compared with their English-speaking counterparts (adjusted odds ratio [OR], 0.29; 95% CI, 0.16 to 0.51). Use of genetic counseling was similar between language groups. Rates of patient portal messaging did not differ between English-speaking and LEP groups on multivariable analysis; however, patients with LEP were less likely to have a portal account (adjusted OR, 0.89; 95% CI, 0.83 to 0.96). Among LEP subgroups, Spanish speakers were significantly less likely to engage with the patient portal compared with English speakers (estimated difference in monthly rate: OR, 0.43; 95% CI, 0.24 to 0.77).We found that patients with LEP had lower rates of clinical trial engagement and odds of electronic patient portal enrollment. Interventions designed to overcome language and cultural barriers are essential to optimize the experience of patients with LEP.

  View details for DOI 10.1200/OP.20.01093

  View details for PubMedID 33844591

• Development and Use of Natural Language Processing for Identification of Distant Cancer Recurrence and Sites of Distant Recurrence Using Unstructured Electronic Health Record Data. JCO clinical cancer informatics Karimi, Y. H., Blayney, D. W., Kurian, A. W., Shen, J. n., Yamashita, R. n., Rubin, D. n., Banerjee, I. n. 2021; 5: 469–78

  Abstract

  Large-scale analysis of real-world evidence is often limited to structured data fields that do not contain reliable information on recurrence status and disease sites. In this report, we describe a natural language processing (NLP) framework that uses data from free-text, unstructured reports to classify recurrence status and sites of recurrence for patients with breast and hepatocellular carcinomas (HCC).Using two cohorts of breast cancer and HCC cases, we validated the ability of a previously developed NLP model to distinguish between no recurrence, local recurrence, and distant recurrence, based on clinician notes, radiology reports, and pathology reports compared with manual curation. A second NLP model was trained and validated to identify sites of recurrence. We compared the ability of each NLP model to identify the presence, timing, and site of recurrence, when compared against manual chart review and International Classification of Diseases coding.A total of 1,273 patients were included in the development and validation of the two models. The NLP model for recurrence detects distant recurrence with an area under the curve of 0.98 (95% CI, 0.96 to 0.99) and 0.95 (95% CI, 0.88 to 0.98) in breast and HCC cohorts, respectively. The mean accuracy of the NLP model for detecting any site of distant recurrence was 0.9 for breast cancer and 0.83 for HCC. The NLP model for recurrence identified a larger proportion of patients with distant recurrence in a breast cancer database (11.1%) compared with International Classification of Diseases coding (2.31%).We developed two NLP models to identify distant cancer recurrence, timing of recurrence, and sites of recurrence based on unstructured electronic health record data. These models can be used to perform large-scale retrospective studies in oncology.

  View details for DOI 10.1200/CCI.20.00165

  View details for PubMedID 33929889

• Weakly supervised temporal model for prediction of breast cancer distant recurrence. Scientific reports Sanyal, J. n., Tariq, A. n., Kurian, A. W., Rubin, D. n., Banerjee, I. n. 2021; 11 (1): 9461

  Abstract

  Efficient prediction of cancer recurrence in advance may help to recruit high risk breast cancer patients for clinical trial on-time and can guide a proper treatment plan. Several machine learning approaches have been developed for recurrence prediction in previous studies, but most of them use only structured electronic health records and only a small training dataset, with limited success in clinical application. While free-text clinic notes may offer the greatest nuance and detail about a patient's clinical status, they are largely excluded in previous predictive models due to the increase in processing complexity and need for a complex modeling framework. In this study, we developed a weak-supervision framework for breast cancer recurrence prediction in which we trained a deep learning model on a large sample of free-text clinic notes by utilizing a combination of manually curated labels and NLP-generated non-perfect recurrence labels. The model was trained jointly on manually curated data from 670 patients and NLP-curated data of 8062 patients. It was validated on manually annotated data from 224 patients with recurrence and achieved 0.94 AUROC. This weak supervision approach allowed us to learn from a larger dataset using imperfect labels and ultimately provided greater accuracy compared to a smaller hand-curated dataset, with less manual effort invested in curation.

  View details for DOI 10.1038/s41598-021-89033-6

  View details for PubMedID 33947927

• A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers. Nature communications Coignard, J. n., Lush, M. n., Beesley, J. n., O'Mara, T. A., Dennis, J. n., Tyrer, J. P., Barnes, D. R., McGuffog, L. n., Leslie, G. n., Bolla, M. K., Adank, M. A., Agata, S. n., Ahearn, T. n., Aittomäki, K. n., Andrulis, I. L., Anton-Culver, H. n., Arndt, V. n., Arnold, N. n., Aronson, K. J., Arun, B. K., Augustinsson, A. n., Azzollini, J. n., Barrowdale, D. n., Baynes, C. n., Becher, H. n., Bermisheva, M. n., Bernstein, L. n., Białkowska, K. n., Blomqvist, C. n., Bojesen, S. E., Bonanni, B. n., Borg, A. n., Brauch, H. n., Brenner, H. n., Burwinkel, B. n., Buys, S. S., Caldés, T. n., Caligo, M. A., Campa, D. n., Carter, B. D., Castelao, J. E., Chang-Claude, J. n., Chanock, S. J., Chung, W. K., Claes, K. B., Clarke, C. L., Collée, J. M., Conroy, D. M., Czene, K. n., Daly, M. B., Devilee, P. n., Diez, O. n., Ding, Y. C., Domchek, S. M., Dörk, T. n., Dos-Santos-Silva, I. n., Dunning, A. M., Dwek, M. n., Eccles, D. M., Eliassen, A. H., Engel, C. n., Eriksson, M. n., Evans, D. G., Fasching, P. A., Flyger, H. n., Fostira, F. n., Friedman, E. n., Fritschi, L. n., Frost, D. n., Gago-Dominguez, M. n., Gapstur, S. M., Garber, J. n., Garcia-Barberan, V. n., García-Closas, M. n., García-Sáenz, J. A., Gaudet, M. M., Gayther, S. A., Gehrig, A. n., Georgoulias, V. n., Giles, G. G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., González-Neira, A. n., Greene, M. H., Guénel, P. n., Haeberle, L. n., Hahnen, E. n., Haiman, C. A., Håkansson, N. n., Hall, P. n., Hamann, U. n., Harrington, P. A., Hart, S. N., He, W. n., Hogervorst, F. B., Hollestelle, A. n., Hopper, J. L., Horcasitas, D. J., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Jager, A. n., Jakubowska, A. n., James, P. A., Jensen, U. B., John, E. M., Jones, M. E., Kaaks, R. n., Kapoor, P. M., Karlan, B. Y., Keeman, R. n., Khusnutdinova, E. n., Kiiski, J. I., Ko, Y. D., Kosma, V. M., Kraft, P. n., Kurian, A. W., Laitman, Y. n., Lambrechts, D. n., Le Marchand, L. n., Lester, J. n., Lesueur, F. n., Lindstrom, T. n., Lopez-Fernández, A. n., Loud, J. T., Luccarini, C. n., Mannermaa, A. n., Manoukian, S. n., Margolin, S. n., Martens, J. W., Mebirouk, N. n., Meindl, A. n., Miller, A. n., Milne, R. L., Montagna, M. n., Nathanson, K. L., Neuhausen, S. L., Nevanlinna, H. n., Nielsen, F. C., O'Brien, K. M., Olopade, O. I., Olson, J. E., Olsson, H. n., Osorio, A. n., Ottini, L. n., Park-Simon, T. W., Parsons, M. T., Pedersen, I. S., Peshkin, B. n., Peterlongo, P. n., Peto, J. n., Pharoah, P. D., Phillips, K. A., Polley, E. C., Poppe, B. n., Presneau, N. n., Pujana, M. A., Punie, K. n., Radice, P. n., Rantala, J. n., Rashid, M. U., Rennert, G. n., Rennert, H. S., Robson, M. n., Romero, A. n., Rossing, M. n., Saloustros, E. n., Sandler, D. P., Santella, R. n., Scheuner, M. T., Schmidt, M. K., Schmidt, G. n., Scott, C. n., Sharma, P. n., Soucy, P. n., Southey, M. C., Spinelli, J. J., Steinsnyder, Z. n., Stone, J. n., Stoppa-Lyonnet, D. n., Swerdlow, A. n., Tamimi, R. M., Tapper, W. J., Taylor, J. A., Terry, M. B., Teulé, A. n., Thull, D. L., Tischkowitz, M. n., Toland, A. E., Torres, D. n., Trainer, A. H., Truong, T. n., Tung, N. n., Vachon, C. M., Vega, A. n., Vijai, J. n., Wang, Q. n., Wappenschmidt, B. n., Weinberg, C. R., Weitzel, J. N., Wendt, C. n., Wolk, A. n., Yadav, S. n., Yang, X. R., Yannoukakos, D. n., Zheng, W. n., Ziogas, A. n., Zorn, K. K., Park, S. K., Thomassen, M. n., Offit, K. n., Schmutzler, R. K., Couch, F. J., Simard, J. n., Chenevix-Trench, G. n., Easton, D. F., Andrieu, N. n., Antoniou, A. C. 2021; 12 (1): 1078

  Abstract

  Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.

  View details for DOI 10.1038/s41467-020-20496-3

  View details for PubMedID 33597508

• Tobacco Smoking and Risk of Second Primary Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Aredo, J. V., Luo, S. J., Gardner, R. M., Sanyal, N. n., Choi, E. n., Hickey, T. P., Riley, T. L., Huang, W. Y., Kurian, A. W., Leung, A. N., Wilkens, L. R., Robbins, H. A., Riboli, E. n., Kaaks, R. n., Tjønneland, A. n., Vermeulen, R. C., Panico, S. n., Le Marchand, L. n., Amos, C. I., Hung, R. J., Freedman, N. D., Johansson, M. n., Cheng, I. n., Wakelee, H. A., Han, S. S. 2021

  Abstract

  Lung cancer survivors are at high risk of a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined risk factors for SPLC across multiple epidemiologic cohorts and assessed the impact of smoking cessation on reducing SPLC risk.We analyzed data from 7,059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, N=3,423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (EPIC, N=4,731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.Overall, 163 (2.3%) MEC cases developed a SPLC. Smoking pack-years (HR 1.18 per 10 pack-years; P<0.001) and smoking intensity (HR 1.30 per 10 cigarettes per day (CPD); P<0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's (USPSTF) screening criteria at IPLC diagnosis also had an increased SPLC risk (HR 1.92; P<0.001). Validation studies with PLCO and EPIC showed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (Pmeta<0.001), 1.25 per 10 CPD (Pmeta<0.001), and 1.99 (Pmeta<0.001) for meeting the USPSTF criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR 0.17; P<0.001).Tobacco smoking is a risk factor for SPLC. Smoking cessation after IPLC diagnosis may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.

  View details for DOI 10.1016/j.jtho.2021.02.024

  View details for PubMedID 33722709

• A Population-Based Study of Genes Previously Implicated in Breast Cancer. The New England journal of medicine Hu, C. n., Hart, S. N., Gnanaolivu, R. n., Huang, H. n., Lee, K. Y., Na, J. n., Gao, C. n., Lilyquist, J. n., Yadav, S. n., Boddicker, N. J., Samara, R. n., Klebba, J. n., Ambrosone, C. B., Anton-Culver, H. n., Auer, P. n., Bandera, E. V., Bernstein, L. n., Bertrand, K. A., Burnside, E. S., Carter, B. D., Eliassen, H. n., Gapstur, S. M., Gaudet, M. n., Haiman, C. n., Hodge, J. M., Hunter, D. J., Jacobs, E. J., John, E. M., Kooperberg, C. n., Kurian, A. W., Le Marchand, L. n., Lindstroem, S. n., Lindstrom, T. n., Ma, H. n., Neuhausen, S. n., Newcomb, P. A., O'Brien, K. M., Olson, J. E., Ong, I. M., Pal, T. n., Palmer, J. R., Patel, A. V., Reid, S. n., Rosenberg, L. n., Sandler, D. P., Scott, C. n., Tamimi, R. n., Taylor, J. A., Trentham-Dietz, A. n., Vachon, C. M., Weinberg, C. n., Yao, S. n., Ziogas, A. n., Weitzel, J. N., Goldgar, D. E., Domchek, S. M., Nathanson, K. L., Kraft, P. n., Polley, E. C., Couch, F. J. 2021

  Abstract

  Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer.This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).

  View details for DOI 10.1056/NEJMoa2005936

  View details for PubMedID 33471974

• Reply to Ritzwoller et al. JCO clinical cancer informatics Karimi, Y. H., Kurian, A. W., Blayney, D. W., Banerjee, I. 2021; 5: 1026-1027

  View details for DOI 10.1200/CCI.21.00145

  View details for PubMedID 34637331

• Multiple imputation with missing data indicators. Statistical methods in medical research Beesley, L. J., Bondarenko, I., Elliot, M. R., Kurian, A. W., Katz, S. J., Taylor, J. M. 2021: 9622802211047346

  Abstract

  Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation, also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we can generalize the sequential regression multiple imputation imputation procedure to handle missingness not at random in the setting where missingness may depend on other variables that are also missing but not on the missing variable itself, conditioning on fully observed variables. We provide algebraic justification for several generalizations of standard sequential regression multiple imputation using Taylor series and other approximations of the target imputation distribution under missingness not at random. Resulting regression model approximations include indicators for missingness, interactions, or other functions of the missingness not at random missingness model and observed data. In a simulation study, we demonstrate that the proposed sequential regression multiple imputation modifications result in reduced bias in the final analysis compared to standard sequential regression multiple imputation, with an approximation strategy involving inclusion of an offset in the imputation model performing the best overall. The method is illustrated in a breast cancer study, where the goal is to estimate the prevalence of a specific genetic pathogenic variant.

  View details for DOI 10.1177/09622802211047346

  View details for PubMedID 34643465

• Predicted Chemotherapy Benefit for Breast Cancer Patients With Germline Pathogenic Variants in Cancer Susceptibility Genes. JNCI cancer spectrum Kurian, A. W., Ward, K. C., Abrahamse, P. n., Hamilton, A. S., Katz, S. J. 2021; 5 (1): pkaa083

  Abstract

  Breast cancer patients increasingly undergo genetic testing. To examine chemotherapy indications for germline pathogenic variant (PV) carriers, we linked results of germline testing to Georgia and California Surveillance, Epidemiology, and End Results registry records, including 21-gene recurrence score (RS) results, for breast cancer patients diagnosed in 2013-2017. All statistical tests were 2-sided. Patients (N=37 349) had RS results of whom 714 had BRCA1, BRCA2, CHEK2, ATM, PALB2, or Lynch syndrome (MLH1, MSH2, MSH6, PMS2) PVs. For women aged 50 years or older at breast cancer diagnosis, RS often exceeded the chemotherapy benefit threshold (≥26) with BRCA1 (71.7% vs 14.4% with none; P <.001), PALB2 (37.1%; P = .001), and BRCA2 (44.3%; P < .001) PVs. Results were similar for women diagnosed at younger than 50 years of age. PVs in BRCA1, but not BRCA2, PALB2, ATM, CHEK2, or Lynch syndrome genes, were associated with elevated RS on multivariable analysis (P < .001). Results may inform RS testing decisions in breast cancer patients with PVs.

  View details for DOI 10.1093/jncics/pkaa083

  View details for PubMedID 33426465

  View details for PubMedCentralID PMC7785044

• Germline pathogenic variants in the Ataxia Telangiectasia Mutated (ATM) gene are associated with high and moderate risks for multiple cancers. Cancer prevention research (Philadelphia, Pa.) Hall, M. J., Bernhisel, R. n., Hughes, E. n., Larson, K. n., Rosenthal, E. T., Singh, N. A., Lancaster, J. M., Kurian, A. W. 2021

  Abstract

  Pathogenic variants (PVs) in ATM are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate ATM PV cancer risks independent of family cancer history. This analysis included patients referred for hereditary cancer testing with a multi-gene panel (N=627,742). Cancer risks for ATM PV carriers (N=4,607) were adjusted for family history using multivariable logistic regression and reported as odds ratios (ORs) with 95% confidence intervals (CIs). Sub-analyses of the c.7271T>G missense PV were conducted. Moderate-to-high risks for pancreatic (OR 4.21; 95% CI 3.24-5.47), prostate (OR 2.58; 95% CI 1.93-3.44), gastric (OR 2.97; 95% CI 1.66-5.31) and invasive ductal breast (OR 2.03; 95% CI 1.89-2.19) cancers were estimated for ATM PV carriers. Notably, c.7271T>G was associated with higher invasive ductal breast cancer risk (OR 3.76, 95% CI 2.76-5.12) than other missense and truncating ATM PVs. Low-to-moderate risks were seen for ductal carcinoma in situ (OR 1.80, 95% CI 1.61-2.02), male breast cancer (OR 1.72, 95% CI 1.08-2.75), ovarian cancer (OR 1.57; 95% CI 1.35-1.83), colorectal cancer (OR 1.49; 95% CI 1.24-1.79) and melanoma (OR 1.46; 95% CI 1.18-1.81). ATM PVs are associated with multiple cancer risks and, while professional society guidelines support that carriers are eligible for increased breast and pancreatic cancer screening, increased screening for prostate and gastric cancer may also be warranted. c.7271T>G is associated with high risk for breast cancer, with a three to four-fold risk increase that supports consideration of strategies for prevention and/or early detection.

  View details for DOI 10.1158/1940-6207.CAPR-20-0448

  View details for PubMedID 33509806

• Association of Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in Women With BRCA1 and BRCA2 Pathogenic Variants. JAMA oncology Choi, Y. H., Terry, M. B., Daly, M. B., MacInnis, R. J., Hopper, J. L., Colonna, S. n., Buys, S. S., Andrulis, I. L., John, E. M., Kurian, A. W., Briollais, L. n. 2021

  Abstract

  Women with pathogenic variants in BRCA1 and BRCA2 are at high risk of developing breast and ovarian cancers. They usually undergo intensive cancer surveillance and may also consider surgical interventions, such as risk-reducing mastectomy or risk-reducing salpingo-oophorectomy (RRSO). Risk-reducing salpingo-oophorectomy has been shown to reduce ovarian cancer risk, but its association with breast cancer risk is less clear.To assess the association of RRSO with the risk of breast cancer in women with BRCA1 and BRCA2 pathogenic variants.This case series included families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried an inherited pathogenic variant in BRCA1 (498 families) or BRCA2 (378 families). A survival analysis approach was used that was designed specifically to assess the time-varying association of RRSO with breast cancer risk and accounting for other potential biases. Data were analyzed from August 2019 to November 2020.Risk-reducing salpingo-oophorectomy.In all analyses, the primary end point was the time to a first primary breast cancer.A total of 876 families were evaluated, including 498 with BRCA1 (2650 individuals; mean [SD] event age, 55.8 [19.1] years; 437 White probands [87.8%]) and 378 with BRCA2 (1925 individuals; mean [SD] event age, 57.0 [18.6] years; 299 White probands [79.1%]). Risk-reducing salpingo-oophorectomy was associated with a reduced risk of breast cancer for BRCA1 and BRCA2 pathogenic variant carriers within 5 years after surgery (hazard ratios [HRs], 0.28 [95% CI, 0.10-0.63] and 0.19 [95% CI, 0.06-0.71], respectively), whereas the corresponding HRs were weaker after 5 years postsurgery (HRs, 0.64 [95% CI, 0.38-0.97] and 0.99 [95% CI; 0.84-1.00], respectively). For BRCA1 and BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years, the cause-specific cumulative risk of breast cancer was 49.7% (95% CI, 40.0-60.3) and 52.7% (95% CI, 47.9-58.7) by age 70 years, respectively, compared with 61.0% (95% CI, 56.7-66.0) and 54.0% (95% CI, 49.3-60.1), respectively, for women without RRSO.Although the primary indication for RRSO is the prevention of ovarian cancer, it is also critical to assess its association with breast cancer risk in order to guide clinical decision-making about RRSO use and timing. The results of this case series suggest a reduced risk of breast cancer associated with RRSO in the immediate 5 years after surgery in women carrying BRCA1 and BRCA2 pathogenic variants, and a longer-term association with cumulative breast cancer risk in women carrying BRCA1 pathogenic variants.

  View details for DOI 10.1001/jamaoncol.2020.7995

  View details for PubMedID 33630024

• Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Daly, M. B., Pal, T. n., Berry, M. P., Buys, S. S., Dickson, P. n., Domchek, S. M., Elkhanany, A. n., Friedman, S. n., Goggins, M. n., Hutton, M. L., Karlan, B. Y., Khan, S. n., Klein, C. n., Kohlmann, W. n., Kurian, A. W., Laronga, C. n., Litton, J. K., Mak, J. S., Menendez, C. S., Merajver, S. D., Norquist, B. S., Offit, K. n., Pederson, H. J., Reiser, G. n., Senter-Jamieson, L. n., Shannon, K. M., Shatsky, R. n., Visvanathan, K. n., Weitzel, J. N., Wick, M. J., Wisinski, K. B., Yurgelun, M. B., Darlow, S. D., Dwyer, M. A. 2021; 19 (1): 77–102

  Abstract

  The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

  View details for DOI 10.6004/jnccn.2021.0001

  View details for PubMedID 33406487

• Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk AMERICAN JOURNAL OF HUMAN GENETICS Kramer, I., Hooning, M. J., Mavaddat, N., Hauptmann, M., Keeman, R., Steyerberg, E. W., Giardiello, D., Antoniou, A. C., Pharoah, P. P., Canisius, S., Abu-Ful, Z., Andrulis, I. L., Anton-Culver, H., Aronson, K. J., Augustinsson, A., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N., Bojesen, S. E., Bolla, M. K., Bonanni, B., Brauch, H., Bremer, M., Brucker, S. Y., Burwinkel, B., Castelao, J. E., Chan, T. L., Chang-Claude, J., Chanock, S. J., Chenevix-Trench, G., Choi, J., Clarke, C. L., Collee, J., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dork, T., dos-Santos-Silva, I., Dunning, A. M., Dwek, M., Eccles, D. M., Evans, D., Fasching, P. A., Flyger, H., Gago-Dominguez, M., Garcia-Closas, M., Garcia-Saenz, J. A., Giles, G. G., Goldgar, D. E., Gonzalez-Neira, A., Haiman, C. A., Hakansson, N., Hamann, U., Hartman, M., Heemskerk-Gerritsen, B. M., Hollestelle, A., Hopper, J. L., Hou, M., Howell, A., Ito, H., Jakimovska, M., Jakubowska, A., Janni, W., John, E. M., Jung, A., Kang, D., Kets, C., Khusnutdinova, E., Ko, Y., Kristensen, V. N., Kurian, A. W., Kwong, A., Lambrechts, D., Le Marchand, L., Li, J., Lindblom, A., Mannermaa, A., Manoochehri, M., Margolin, S., Matsuo, K., Mavroudis, D., Meindl, A., Milne, R. L., Mulligan, A., Muranen, T. A., Neuhausen, S. L., Nevanlinna, H., Newman, W. G., Olshan, A. F., Olson, J. E., Olsson, H., Park-Simon, T., Peto, J., Petridis, C., Plaseska-Karanfilska, D., Presneau, N., Pylkas, K., Radice, P., Rennert, G., Romero, A., Roylance, R., Saloustros, E., Sawyer, E. J., Schmutzler, R. K., Schwentner, L., Scott, C., See, M., Shah, M., Shen, C., Shu, X., Siesling, S., Slager, S., Sohn, C., Southey, M. C., Spinelli, J. J., Stone, J., Tapper, W. J., Tengstrom, M., Teo, S., Terry, M., Tollenaar, R. M., Tomlinson, I., Troester, M. A., Vachon, C. M., van Ongeval, C., van Veen, E. M., Winqvist, R., Wolk, A., Zheng, W., Ziogas, A., Easton, D. F., Hall, P., Schmidt, M. K., NBCS Collaborators, ABCTB Investigators, kConFab Investigators 2020; 107 (5): 837–48

  View details for Web of Science ID 000587855200005

• Trends in germline genetic testing and results into survivorship for women diagnosed with breast cancer or ovarian cancer, 2013 to 2017. Katz, S. J., Morrow, M., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000607202800270

• Real-world outcomes of patients with metastatic breast cancer (BC) treated with osteoclast inhibitors (OIs). Karimi, Y., Purington, N., Liu, M., Kurian, A. W., Sledge, G. W., Blayney, D. W. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307247

• Linking insurance claims across time to characterize treatment, monitoring, and end-of-life care in metastatic breast cancer. Caswell-Jin, J., Callahan, A., Purington, N., Han, S. S., Itakura, H., Sledge, G. W., Shah, N., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368303141

• Comprehensive breast cancer (BC) risk assessment for CHEK2 carriers incorporating a polygenic risk score (PRS) and the Tyrer-Cuzick (TC) model. Gallagher, S., Hughes, E., Kurian, A. W., Domchek, S. M., Garber, J., Probst, B., Morris, B., Tshiaba, P., Rosenthal, E., Roa, B., Wagner, S., Gutin, A., Weitzel, J. N., Lanchbury, J., Robson, M. E. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301028

• Development and validation of natural language processing (NLP) algorithm for detection of distant versus local breast cancer recurrence and metastatic site. Karimi, Y., Blayney, D. W., Kurian, A. W., Rubin, D., Banerjee, I. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301153

• Performance of the IBIS/Tyrer-Cuzick (TC) Model by race/ethnicity in the Women's Health Initiative. Kurian, A. W., Hughes, E., Bernhisel, R., Probst, B., Lanchbury, J., Wagner, S., Gutin, A., Caswell-Jin, J., Rohan, T. E., Shadyab, A. H., Manson, J. E., Lane, D., Stefanick, M. L. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301027

• Clinicopathologic features of invasive breast cancer (BC) diagnosed in carriers of germline PALB2, CHEK2 and ATM pathogenic variants. Scott, D., Kingham, K., Hodan, R., Ma, C., Mills, M., Ford, J. M., Kurian, A. W., Telli, M. L. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301071

• DO RESEARCH PARTICIPANTS DIFFER BY RECRUITMENT SOURCE?OBSERVATIONS FROM A STUDY OF NEWLY-DIAGNOSED BREAST CANCER PATIENTS Agrawal, A., Benedict, C., Nouriani, B., Medina, J., Kurian, A. W., Spiegel, D. OXFORD UNIV PRESS INC. 2020: S75

  View details for Web of Science ID 000546262400156

• Insights From a Temporal Assessment of Increases in US Private Payer Coverage of Tumor Sequencing From 2015 to 2019. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Trosman, J. R., Douglas, M. P., Liang, S. Y., Weldon, C. B., Kurian, A. W., Kelley, R. K., Phillips, K. A. 2020; 23 (5): 551-558

  Abstract

  To examine the temporal trajectory of insurance coverage for next-generation tumor sequencing (sequencing) by private US payers, describe the characteristics of coverage adopters and nonadopters, and explore adoption trends relative to the Centers for Medicare and Medicaid Services' National Coverage Determination (CMS NCD) for sequencing.We identified payers with positive coverage (adopters) or negative coverage (nonadopters) of sequencing on or before April 1, 2019, and abstracted their characteristics including size, membership in the BlueCross BlueShield Association, and whether they used a third-party policy. Using descriptive statistics, payer characteristics were compared between adopters and nonadopters and between pre-NCD and post-NCD adopters. An adoption timeline was constructed.Sixty-nine payers had a sequencing policy. Positive coverage started November 30, 2015, with 1 payer and increased to 33 (48%) as of April 1, 2019. Adopters were less likely to be BlueCross BlueShield members (P < .05) and more likely to use a third-party policy (P < .001). Fifty-eight percent of adopters were small payers. Among adopters, 52% initiated coverage pre-NCD over a 25-month period and 48% post-NCD over 17 months.We found an increase, but continued variability, in coverage over 3.5 years. Temporal analyses revealed important trends: the possible contribution of the CMS NCD to a faster pace of coverage adoption, the interdependence in coverage timing among BlueCross BlueShield members, the impact of using a third-party policy on coverage timing, and the importance of small payers in early adoption. Our study is a step toward systematic temporal research of coverage for precision medicine, which will inform policy and affordability assessments.

  View details for DOI 10.1016/j.jval.2020.01.018

  View details for PubMedID 32389219

• Projected Reductions in Absolute Cancer-Related Deaths from Diagnosing Cancers Before Metastasis, 2006-2015. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Clarke, C. A., Hubbell, E., Kurian, A. W., Colditz, G. A., Hartman, A. R., Gomez, S. L. 2020

  Abstract

  New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer-related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.We obtained stage-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for 17 cancer types for all persons diagnosed ages 50 to 79 years in 18 geographic regions between 2006 and 2015. For a hypothetical cohort of 100,000 persons, we estimated cancer-related deaths under assumptions that cancers diagnosed at stage IV were diagnosed at earlier stages.Stage IV cancers represented 18% of all estimated diagnoses but 48% of all estimated cancer-related deaths within 5 years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15% of all cancer-related deaths. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in all-cause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease.Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality.Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit.

  View details for DOI 10.1158/1055-9965.EPI-19-1366

  View details for PubMedID 32229577

• Abstract P5-03-02: Cancer risks associated with pathogenic variants in the ataxia telangiectasia mutated (ATM) gen San Antonio Breast Cancer Symposium Hall, M., Larson, K., Bernhisel, R., Hughes, E., Rosenthal, E., Singh, N., Lancaster, J. M., Kurian, A. W. 2020

  View details for DOI 10.1158/1538-7445.SABCS19-P5-03-02

• Pathogenic Variants in Breast Cancer Susceptibility Genes in Older Women-Reply. JAMA Kurian, A. W., Bernhisel, R. n., Stefanick, M. L. 2020; 324 (4): 397–98

  View details for DOI 10.1001/jama.2020.7999

  View details for PubMedID 32721001

• Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants. Nature communications Shu, X. n., Long, J. n., Cai, Q. n., Kweon, S. S., Choi, J. Y., Kubo, M. n., Park, S. K., Bolla, M. K., Dennis, J. n., Wang, Q. n., Yang, Y. n., Shi, J. n., Guo, X. n., Li, B. n., Tao, R. n., Aronson, K. J., Chan, K. Y., Chan, T. L., Gao, Y. T., Hartman, M. n., Kee Ho, W. n., Ito, H. n., Iwasaki, M. n., Iwata, H. n., John, E. M., Kasuga, Y. n., Soon Khoo, U. n., Kim, M. K., Kong, S. Y., Kurian, A. W., Kwong, A. n., Lee, E. S., Li, J. n., Lophatananon, A. n., Low, S. K., Mariapun, S. n., Matsuda, K. n., Matsuo, K. n., Muir, K. n., Noh, D. Y., Park, B. n., Park, M. H., Shen, C. Y., Shin, M. H., Spinelli, J. J., Takahashi, A. n., Tseng, C. n., Tsugane, S. n., Wu, A. H., Xiang, Y. B., Yamaji, T. n., Zheng, Y. n., Milne, R. L., Dunning, A. M., Pharoah, P. D., García-Closas, M. n., Teo, S. H., Shu, X. O., Kang, D. n., Easton, D. F., Simard, J. n., Zheng, W. n. 2020; 11 (1): 1217

  Abstract

  Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.

  View details for DOI 10.1038/s41467-020-15046-w

  View details for PubMedID 32139696

  View details for PubMedCentralID PMC7057957

• European polygenic risk score for prediction of breast cancer shows similar performance in Asian women. Nature communications Ho, W. K., Tan, M. M., Mavaddat, N. n., Tai, M. C., Mariapun, S. n., Li, J. n., Ho, P. J., Dennis, J. n., Tyrer, J. P., Bolla, M. K., Michailidou, K. n., Wang, Q. n., Kang, D. n., Choi, J. Y., Jamaris, S. n., Shu, X. O., Yoon, S. Y., Park, S. K., Kim, S. W., Shen, C. Y., Yu, J. C., Tan, E. Y., Chan, P. M., Muir, K. n., Lophatananon, A. n., Wu, A. H., Stram, D. O., Matsuo, K. n., Ito, H. n., Chan, C. W., Ngeow, J. n., Yong, W. S., Lim, S. H., Lim, G. H., Kwong, A. n., Chan, T. L., Tan, S. M., Seah, J. n., John, E. M., Kurian, A. W., Koh, W. P., Khor, C. C., Iwasaki, M. n., Yamaji, T. n., Tan, K. M., Tan, K. T., Spinelli, J. J., Aronson, K. J., Hasan, S. N., Rahmat, K. n., Vijayananthan, A. n., Sim, X. n., Pharoah, P. D., Zheng, W. n., Dunning, A. M., Simard, J. n., van Dam, R. M., Yip, C. H., Taib, N. A., Hartman, M. n., Easton, D. F., Teo, S. H., Antoniou, A. C. 2020; 11 (1): 3833

  Abstract

  Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

  View details for DOI 10.1038/s41467-020-17680-w

  View details for PubMedID 32737321

• A case of a trans-masculine patient receiving testosterone with a history of estrogen receptor-positive breast cancer. The breast journal Eckhert, E. n., Laniakea, B. n., Kurian, A. W. 2020

  View details for DOI 10.1111/tbj.13829

  View details for PubMedID 32255524

• NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020. Journal of the National Comprehensive Cancer Network : JNCCN Daly, M. B., Pilarski, R. n., Yurgelun, M. B., Berry, M. P., Buys, S. S., Dickson, P. n., Domchek, S. M., Elkhanany, A. n., Friedman, S. n., Garber, J. E., Goggins, M. n., Hutton, M. L., Khan, S. n., Klein, C. n., Kohlmann, W. n., Kurian, A. W., Laronga, C. n., Litton, J. K., Mak, J. S., Menendez, C. S., Merajver, S. D., Norquist, B. S., Offit, K. n., Pal, T. n., Pederson, H. J., Reiser, G. n., Shannon, K. M., Visvanathan, K. n., Weitzel, J. N., Wick, M. J., Wisinski, K. B., Dwyer, M. A., Darlow, S. D. 2020; 18 (4): 380–91

  Abstract

  The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.

  View details for DOI 10.6004/jnccn.2020.0017

  View details for PubMedID 32259785

• Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. Scientific reports Liu, J. n., Prager-van der Smissen, W. J., Collée, J. M., Bolla, M. K., Wang, Q. n., Michailidou, K. n., Dennis, J. n., Ahearn, T. U., Aittomäki, K. n., Ambrosone, C. B., Andrulis, I. L., Anton-Culver, H. n., Antonenkova, N. N., Arndt, V. n., Arnold, N. n., Aronson, K. J., Augustinsson, A. n., Auvinen, P. n., Becher, H. n., Beckmann, M. W., Behrens, S. n., Bermisheva, M. n., Bernstein, L. n., Bogdanova, N. V., Bogdanova-Markov, N. n., Bojesen, S. E., Brauch, H. n., Brenner, H. n., Briceno, I. n., Brucker, S. Y., Brüning, T. n., Burwinkel, B. n., Cai, Q. n., Cai, H. n., Campa, D. n., Canzian, F. n., Castelao, J. E., Chang-Claude, J. n., Chanock, S. J., Choi, J. Y., Christiaens, M. n., Clarke, C. L., Couch, F. J., Czene, K. n., Daly, M. B., Devilee, P. n., Dos-Santos-Silva, I. n., Dwek, M. n., Eccles, D. M., Eliassen, A. H., Fasching, P. A., Figueroa, J. n., Flyger, H. n., Fritschi, L. n., Gago-Dominguez, M. n., Gapstur, S. M., García-Closas, M. n., García-Sáenz, J. A., Gaudet, M. M., Giles, G. G., Goldberg, M. S., Goldgar, D. E., Guénel, P. n., Haiman, C. A., Håkansson, N. n., Hall, P. n., Harrington, P. A., Hart, S. N., Hartman, M. n., Hillemanns, P. n., Hopper, J. L., Hou, M. F., Hunter, D. J., Huo, D. n., Ito, H. n., Iwasaki, M. n., Jakimovska, M. n., Jakubowska, A. n., John, E. M., Kaaks, R. n., Kang, D. n., Keeman, R. n., Khusnutdinova, E. n., Kim, S. W., Kraft, P. n., Kristensen, V. N., Kurian, A. W., Le Marchand, L. n., Li, J. n., Lindblom, A. n., Lophatananon, A. n., Luben, R. N., Lubiński, J. n., Mannermaa, A. n., Manoochehri, M. n., Manoukian, S. n., Margolin, S. n., Mariapun, S. n., Matsuo, K. n., Maurer, T. n., Mavroudis, D. n., Meindl, A. n., Menon, U. n., Milne, R. L., Muir, K. n., Mulligan, A. M., Neuhausen, S. L., Nevanlinna, H. n., Offit, K. n., Olopade, O. I., Olson, J. E., Olsson, H. n., Orr, N. n., Park, S. K., Peterlongo, P. n., Peto, J. n., Plaseska-Karanfilska, D. n., Presneau, N. n., Rack, B. n., Rau-Murthy, R. n., Rennert, G. n., Rennert, H. S., Rhenius, V. n., Romero, A. n., Ruebner, M. n., Saloustros, E. n., Schmutzler, R. K., Schneeweiss, A. n., Scott, C. n., Shah, M. n., Shen, C. Y., Shu, X. O., Simard, J. n., Sohn, C. n., Southey, M. C., Spinelli, J. J., Tamimi, R. M., Tapper, W. J., Teo, S. H., Terry, M. B., Torres, D. n., Truong, T. n., Untch, M. n., Vachon, C. M., van Asperen, C. J., Wolk, A. n., Yamaji, T. n., Zheng, W. n., Ziogas, A. n., Ziv, E. n., Torres-Mejía, G. n., Dörk, T. n., Swerdlow, A. J., Hamann, U. n., Schmidt, M. K., Dunning, A. M., Pharoah, P. D., Easton, D. F., Hooning, M. J., Martens, J. W., Hollestelle, A. n. 2020; 10 (1): 9688

  Abstract

  In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

  View details for DOI 10.1038/s41598-020-65665-y

  View details for PubMedID 32546843

• Hospital Characteristics and Breast Cancer Survival in the California Breast Cancer Survivorship Consortium. JCO oncology practice Shariff-Marco, S. n., Ellis, L. n., Yang, J. n., Koo, J. n., John, E. M., Keegan, T. H., Cheng, I. n., Monroe, K. R., Vigen, C. n., Kwan, M. L., Lu, Y. n., Bernstein, L. n., Wu, A. H., Gomez, S. L., Kurian, A. W. 2020; 16 (6): e517–e528

  Abstract

  Racial/ethnic disparities in breast cancer survival are well documented, but the influence of health care institutions is unclear. We therefore examined the effect of hospital characteristics on survival.Harmonized data pooled from 5 case-control and prospective cohort studies within the California Breast Cancer Survivorship Consortium were linked to the California Cancer Registry and the California Neighborhoods Data System. The study included 9,701 patients with breast cancer who were diagnosed between 1993 and 2007. First reporting hospitals were classified by hospital type-National Cancer Institute (NCI) -designated cancer center, American College of Surgeons (ACS) Cancer Program, other-and hospital composition of the neighborhood socioeconomic status and race/ethnicity of patients with cancer. Multivariable Cox proportional hazards models adjusted for clinical and patient-level prognostic factors were used to examine the influence of hospital characteristics on survival.Fewer than one half of women received their initial care at an NCI-designated cancer center (5%) or ACS program (38%) hospital. Receipt of initial care in ACS program hospitals varied by race/ethnicity-highest among non-Latina White patients (45%), and lowest among African Americans (21%). African-American women had superior breast cancer survival when receiving initial care in ACS hospitals versus other hospitals (non-ACS program and non-NCI-designated cancer center; hazard ratio, 0.67; 95% CI, 0.55 to 0.83). Other hospital characteristics were not associated with survival.African American women may benefit significantly from breast cancer care in ACS program hospitals; however, most did not receive initial care at such facilities. Future research should identify the aspects of ACS program hospitals that are associated with higher survival and evaluate strategies by which to enhance access to and use of high-quality hospitals, particularly among African American women.

  View details for DOI 10.1200/OP.20.00064

  View details for PubMedID 32521220

• Health Disparities in Germline Genetic Testing for Cancer Susceptibility Current Breast Cancer Reports Parikh, D. A., Dickerson, J. C., Kurian, A. W. 2020

  View details for DOI 10.1007/s12609-020-00354-3

• Combined associations of a polygenic risk score and classical risk factors with breast cancer risk. Journal of the National Cancer Institute Kapoor, P. M., Mavaddat, N. n., Choudhury, P. P., Wilcox, A. N., Lindström, S. n., Behrens, S. n., Michailidou, K. n., Dennis, J. n., Bolla, M. K., Wang, Q. n., Jung, A. n., Abu-Ful, Z. n., Ahearn, T. n., Andrulis, I. L., Anton-Culver, H. n., Arndt, V. n., Aronson, K. J., Auer, P. L., Freeman, L. E., Becher, H. n., Beckmann, M. W., Beeghly-Fadiel, A. n., Benitez, J. n., Bernstein, L. n., Bojesen, S. E., Brauch, H. n., Brenner, H. n., Brüning, T. n., Cai, Q. n., Campa, D. n., Canzian, F. n., Carracedo, A. n., Carter, B. D., Castelao, J. E., Chanock, S. J., Chatterjee, N. n., Chenevix-Trench, G. n., Clarke, C. L., Couch, F. J., Cox, A. n., Cross, S. S., Czene, K. n., Dai, J. Y., Earp, H. S., Ekici, A. B., Eliassen, A. H., Eriksson, M. n., Evans, D. G., Fasching, P. A., Figueroa, J. n., Fritschi, L. n., Gabrielson, M. n., Gago-Dominguez, M. n., Gao, C. n., Gapstur, S. M., Gaudet, M. M., Giles, G. G., González-Neira, A. n., Guénel, P. n., Haeberle, L. n., Haiman, C. A., Håkansson, N. n., Hall, P. n., Hamann, U. n., Hatse, S. n., Heyworth, J. n., Holleczek, B. n., Hoover, R. N., Hopper, J. L., Howell, A. n., Hunter, D. J., John, E. M., Jones, M. E., Kaaks, R. n., Keeman, R. n., Kitahara, C. M., Ko, Y. D., Koutros, S. n., Kurian, A. W., Lambrechts, D. n., Marchand, L. L., Lee, E. n., Lejbkowicz, F. n., Linet, M. n., Lissowska, J. n., Llaneza, A. n., MacInnis, R. J., Martinez, M. E., Maurer, T. n., McLean, C. n., Neuhausen, S. L., Newman, W. G., Norman, A. n., O'Brien, K. M., Olshan, A. F., Olson, J. E., Olsson, H. n., Orr, N. n., Perou, C. M., Pita, G. n., Polley, E. C., Prentice, R. L., Rennert, G. n., Rennert, H. S., Ruddy, K. J., Sandler, D. P., Saunders, C. n., Schoemaker, M. J., Schöttker, B. n., Schumacher, F. n., Scott, C. n., Scott, R. J., Shu, X. O., Smeets, A. n., Southey, M. C., Spinelli, J. J., Stone, J. n., Swerdlow, A. J., Tamimi, R. M., Taylor, J. A., Troester, M. A., Vachon, C. M., van Veen, E. M., Wang, X. n., Weinberg, C. R., Weltens, C. n., Willett, W. n., Winham, S. J., Wolk, A. n., Yang, X. R., Zheng, W. n., Ziogas, A. n., Dunning, A. M., Pharoah, P. D., Schmidt, M. K., Kraft, P. n., Easton, D. F., Milne, R. L., García-Closas, M. n., Chang-Claude, J. n. 2020

  Abstract

  We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history), and on average 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

  View details for DOI 10.1093/jnci/djaa056

  View details for PubMedID 32359158

• Association of a Polygenic Risk Score With Breast Cancer Among Women Carriers of High- and Moderate-Risk Breast Cancer Genes. JAMA network open Gallagher, S. n., Hughes, E. n., Wagner, S. n., Tshiaba, P. n., Rosenthal, E. n., Roa, B. B., Kurian, A. W., Domchek, S. M., Garber, J. n., Lancaster, J. n., Weitzel, J. N., Gutin, A. n., Lanchbury, J. S., Robson, M. n. 2020; 3 (7): e208501

  Abstract

  To date, few studies have examined the extent to which polygenic single-nucleotide variation (SNV) (formerly single-nucleotide polymorphism) scores modify risk for carriers of pathogenic variants (PVs) in breast cancer susceptibility genes. In previous reports, polygenic risk modification was reduced for BRCA1 and BRCA2 PV carriers compared with noncarriers, but limited information is available for carriers of CHEK2, ATM, or PALB2 PVs.To examine an 86-SNV polygenic risk score (PRS) for BRCA1, BRCA2, CHEK2, ATM, and PALB2 PV carriers.A retrospective case-control study using data on 150 962 women tested with a multigene hereditary cancer panel between July 19, 2016, and January 11, 2019, was conducted in a commercial testing laboratory. Participants included women of European ancestry between the ages of 18 and 84 years.Multivariable logistic regression was used to examine the association of the 86-SNV score with invasive breast cancer after adjusting for age, ancestry, and personal and/or family cancer history. Effect sizes, expressed as standardized odds ratios (ORs) with 95% CIs, were assessed for carriers of PVs in each gene as well as for noncarriers.The median age at hereditary cancer testing of the population was 48 years (range, 18-84 years); there were 141 160 noncarriers in addition to carriers of BRCA1 (n = 2249), BRCA2 (n = 2638), CHEK2 (n = 2564), ATM (n = 1445), and PALB2 (n = 906) PVs included in the analysis. The 86-SNV score was associated with breast cancer risk in each of the carrier populations (P < 1 × 10-4). Stratification was more pronounced for noncarriers (OR, 1.47; 95% CI, 1.45-1.49) and CHEK2 PV carriers (OR, 1.49; 95% CI, 1.36-1.64) than for carriers of BRCA1 (OR, 1.20; 95% CI, 1.10-1.32) or BRCA2 (OR, 1.23; 95% CI, 1.12-1.34) PVs. Odds ratios for ATM (OR, 1.37; 95% CI, 1.21-1.55) and PALB2 (OR, 1.34; 95% CI, 1.16-1.55) PV carrier populations were intermediate between those for BRCA1/2 and CHEK2 noncarriers.In this study, the 86-SNV score was associated with modified risk for carriers of BRCA1, BRCA2, CHEK2, ATM, and PALB2 PVs. This finding supports previous reports of reduced PRS stratification for BRCA1 and BRCA2 PV carriers compared with noncarriers. Modification of risk in CHEK2 carriers associated with the 86-SNV score appeared to be similar to that observed in women without a PV. Larger studies are needed to provide more refined estimates of polygenic modification of risk for women with PVs in other moderate-penetrance genes.

  View details for DOI 10.1001/jamanetworkopen.2020.8501

  View details for PubMedID 32609350

• Reply to Residual confounding threatens the validity of observational studies on breast cancer local therapy. Cancer Kurian, A. W., Canchola, A. J., Gomez, S. L. 2020

  View details for DOI 10.1002/cncr.32743

  View details for PubMedID 31999833

• Prevalence of Lynch syndrome in women with mismatch repair-deficient ovarian cancer. Cancer medicine Hodan, R. n., Kingham, K. n., Cotter, K. n., Folkins, A. K., Kurian, A. W., Ford, J. M., Longacre, T. n. 2020

  Abstract

  There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR-D) by immunohistochemistry (IHC).Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR-D by IHC. The incidence of LS in this cohort was evaluated.MMR-D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%-8.3%) primary ovarian-related cancers. Most cases with MMR-D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%-86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%-72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%-50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%-37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%-37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%-86.5%) were confirmed to have LS.Most ovarian cancers with somatic MMR-D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non-Lynch germline mutation identified in this cohort.

  View details for DOI 10.1002/cam4.3688

  View details for PubMedID 33369189

• Racial/ethnic disparities in survival after breast cancer diagnosis by estrogen and progesterone receptor status: A pooled analysis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology John, E. M., McGuire, V. n., Kurian, A. W., Koo, J. n., Shariff-Marco, S. n., Gomez, S. L., Cheng, I. n., Keegan, T. H., Kwan, M. L., Bernstein, L. n., Vigen, C. n., Wu, A. H. 2020

  Abstract

  Limited studies have investigated racial/ethnic survival disparities for breast cancer (BC) defined by estrogen receptor (ER) and progesterone receptor (PR) status in a multiethnic population.Using multivariable Cox proportional hazards models, we assessed associations of race/ethnicity with ER/PR-specific BC mortality in 10,366 Californian women diagnosed with BC from 1993-2009. We evaluated joint associations of race/ethnicity, healthcare, sociodemographic, and lifestyle factors with mortality.Among women with ER/PR+ BC, BC-specific mortality was similar among Hispanic and Asian American women, but higher among African American women (hazard ratio (HR) 1.31, 95% confidence interval 1.05-1.63) compared to non-Hispanic White (NHW) women. BC-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, BC-specific mortality was higher among those treated at non-accredited hospitals (HR 1.57, CI 1.21-2.04) and those from lower SES neighborhoods (HR 1.48, CI 1.16-1.88) compared to NHW women without these characteristics. BC-specific mortality was higher among African American women with at least some college education (HR 1.42, CI 1.11-1.82) compared to NHW women with similar education. For ER-/PR- disease, BC-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with BC-specific mortality varied only by neighborhood SES among African American women.Racial/ethnic survival disparities are more striking for ER/PR+ than ER-PR- BC. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR+ BC.Addressing these factors may help reduce the higher mortality of African American women with ER/PR+ BC.

  View details for DOI 10.1158/1055-9965.EPI-20-1291

  View details for PubMedID 33355191

• Development and Validation of a Clinical Polygenic Risk Score to Predict Breast Cancer Risk. JCO precision oncology Hughes, E. n., Tshiaba, P. n., Gallagher, S. n., Wagner, S. n., Judkins, T. n., Roa, B. n., Rosenthal, E. n., Domchek, S. n., Garber, J. n., Lancaster, J. n., Weitzel, J. n., Kurian, A. W., Lanchbury, J. S., Gutin, A. n., Robson, M. n. 2020; 4

  Abstract

  Women with a family history of breast cancer are frequently referred for hereditary cancer genetic testing, yet < 10% are found to have pathogenic variants in known breast cancer susceptibility genes. Large-scale genotyping studies have identified common variants (primarily single-nucleotide polymorphisms [SNPs]) with individually modest breast cancer risk that, in aggregate, account for considerable breast cancer susceptibility. Here, we describe the development and empirical validation of an SNP-based polygenic breast cancer risk score.A panel of 94 SNPs was examined for association with breast cancer in women of European ancestry undergoing hereditary cancer genetic testing and negative for pathogenic variants in breast cancer susceptibility genes. Candidate polygenic risk scores (PRSs) as predictors of personal breast cancer history were developed through multivariable logistic regression models adjusted for age, cancer history, and ancestry. An optimized PRS was validated in 2 independent cohorts (n = 13,174; n = 141,160).Within the training cohort (n = 24,259), 4,291 women (18%) had a personal history of breast cancer and 8,725 women (36%) reported breast cancer in a first-degree relative. The optimized PRS included 86 variants and was highly predictive of breast cancer status in both validation cohorts (P = 6.4 × 10-66; P < 10-325). The odds ratio (OR) per unit standard deviation was consistent between validations (OR, 1.45 [95% CI, 1.39 to 1.52]; OR 1.47 [95% CI, 1.45 to 1.49]). In a direct comparison, the 86-SNP PRS outperformed a previously described PRS of 77 SNPs.The validation and implementation of a PRS for women without pathogenic variants in known breast cancer susceptibility genes offers potential for risk stratification to guide surveillance recommendations.

  View details for DOI 10.1200/PO.19.00360

  View details for PubMedID 32923876

  View details for PubMedCentralID PMC7446363

• Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients. Cancer Culver, J. O., Ricker, C. N., Bonner, J. n., Kidd, J. n., Sturgeon, D. n., Hodan, R. n., Kingham, K. n., Lowstuter, K. n., Chun, N. M., Lebensohn, A. P., Rowe-Teeter, C. n., Levonian, P. n., Partynski, K. n., Lara-Otero, K. n., Hong, C. n., Morales Pichardo, J. n., Mills, M. A., Brown, K. n., Lerman, C. n., Ladabaum, U. n., McDonnell, K. J., Ford, J. M., Gruber, S. B., Kurian, A. W., Idos, G. E. 2020

  Abstract

  Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs).Study participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA).The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences.In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

  View details for DOI 10.1002/cncr.33357

  View details for PubMedID 33320347

• Patterns of social media use and associations with psychosocial outcomes among breast and gynecologic cancer survivors. Journal of cancer survivorship : research and practice Tolby, L. T., Hofmeister, E. N., Fisher, S. n., Chao, S. n., Benedict, C. n., Kurian, A. W., Berek, J. S., Schapira, L. n., Palesh, O. G. 2020

  Abstract

  We sought to characterize the use of social media (SM) among breast and gynecologic cancer survivors, as well as associations between patterns of SM use and psychosocial outcomes.Two hundred seventy-three breast and gynecologic cancer survivors recruited at the Stanford Women's Cancer Center completed the study. Participants completed questionnaires to measure quality of life (FACT-G), functional social support (Duke-UNC FSSQ), distress (PHQ-4), decision regret (DRS), and SM use.In total, 75.8% of the sample reported using SM. There was no difference in quality of life (QOL), functional social support (FSS), distress, or decision regret between SM users and non-users. SM users indicated using SM for social support (34.3%) and loneliness (24.6%) more than for information-seeking (15.9%), coping (18.8%), or self-disclosure (14%). SM use for coping was associated with lower QOL (p < .001), lower FSS (p < .001), and higher decision regret (p = .029). Use for social support was associated with lower FSS (p = .029). Use for information seeking was associated with lower QOL (p = .012). Use of SM when lonely was associated with lower QOL (p < .001), higher distress (p = .007), lower FSS (p < .001), and higher decision regret (p = .020).Associations between SM use and psychosocial outcomes are nuanced and dependent on motivation for use. Further research is needed to better characterize SM use and associations with psychosocial outcomes among cancer survivors.SM is an important potential avenue for understanding and addressing the psychosocial effects associated with cancer survivorship.

  View details for DOI 10.1007/s11764-020-00959-8

  View details for PubMedID 33161562

• Comparing Five-Year and Lifetime Risks of Breast Cancer in the Prospective Family Study Cohort. Journal of the National Cancer Institute MacInnis, R. J., Knight, J. A., Chung, W. K., Milne, R. L., Whittemore, A. S., Buchsbaum, R. n., Liao, Y. n., Zeinomar, N. n., Dite, G. S., Southey, M. C., Goldgar, D. n., Giles, G. G., Kurian, A. W., Andrulis, I. L., John, E. M., Daly, M. B., Buys, S. S., Phillips, K. A., Hopper, J. L., Terry, M. B. 2020

  Abstract

  Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age.We used the Prospective Family Cohort Study of 14,657 women without breast cancer at baseline in which, during a median follow-up of 10 years, 482 women were diagnosed with invasive breast cancer. We examined the performances of the IBIS and BOADICEA risk models when using alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. All statistical tests were two-sided.Using IBIS, the areas under the receiver-operating characteristic curves were 0.66 (95% confidence interval = 0.63 to 0.68) and 0.56 (95% confidence interval = 0.54 to 0.59) for 5-year and lifetime risks, respectively (Pdiff<0.001). For equivalent sensitivities, the 5-year incidence almost always had higher specificities than lifetime risk from birth. For women aged 20-39 years, 5-year risk performed better than lifetime risk from birth. For women aged 40 years or more, receiver-operating characteristic curves were similar for 5-year and lifetime IBIS risk from birth. Classifications based on remaining lifetime risk were inferior to 5-year risk estimates. Results were similar using BOADICEA.Our analysis shows that risk stratification using clinical models will likely be more accurate when based on predicted 5-year risk compared with risks based on predicted lifetime and remaining lifetime, particularly for women aged 20-39 years.

  View details for DOI 10.1093/jnci/djaa178

  View details for PubMedID 33301022

• Emerging Opportunity of Cascade Genetic Testing for Population-Wide Cancer Prevention and Control. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurian, A. W., Katz, S. J. 2020: JCO2000140

  View details for DOI 10.1200/JCO.20.00140

  View details for PubMedID 32097078

• Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). JAMA oncology Silvestri, V. n., Leslie, G. n., Barnes, D. R., Agnarsson, B. A., Aittomäki, K. n., Alducci, E. n., Andrulis, I. L., Barkardottir, R. B., Barroso, A. n., Barrowdale, D. n., Benitez, J. n., Bonanni, B. n., Borg, A. n., Buys, S. S., Caldés, T. n., Caligo, M. A., Capalbo, C. n., Campbell, I. n., Chung, W. K., Claes, K. B., Colonna, S. V., Cortesi, L. n., Couch, F. J., de la Hoya, M. n., Diez, O. n., Ding, Y. C., Domchek, S. n., Easton, D. F., Ejlertsen, B. n., Engel, C. n., Evans, D. G., Feliubadalò, L. n., Foretova, L. n., Fostira, F. n., Géczi, L. n., Gerdes, A. M., Glendon, G. n., Godwin, A. K., Goldgar, D. E., Hahnen, E. n., Hogervorst, F. B., Hopper, J. L., Hulick, P. J., Isaacs, C. n., Izquierdo, A. n., James, P. A., Janavicius, R. n., Jensen, U. B., John, E. M., Joseph, V. n., Konstantopoulou, I. n., Kurian, A. W., Kwong, A. n., Landucci, E. n., Lesueur, F. n., Loud, J. T., Machackova, E. n., Mai, P. L., Majidzadeh-A, K. n., Manoukian, S. n., Montagna, M. n., Moserle, L. n., Mulligan, A. M., Nathanson, K. L., Nevanlinna, H. n., Ngeow Yuen Ye, J. n., Nikitina-Zake, L. n., Offit, K. n., Olah, E. n., Olopade, O. I., Osorio, A. n., Papi, L. n., Park, S. K., Pedersen, I. S., Perez-Segura, P. n., Petersen, A. H., Pinto, P. n., Porfirio, B. n., Pujana, M. A., Radice, P. n., Rantala, J. n., Rashid, M. U., Rosenzweig, B. n., Rossing, M. n., Santamariña, M. n., Schmutzler, R. K., Senter, L. n., Simard, J. n., Singer, C. F., Solano, A. R., Southey, M. C., Steele, L. n., Steinsnyder, Z. n., Stoppa-Lyonnet, D. n., Tan, Y. Y., Teixeira, M. R., Teo, S. H., Terry, M. B., Thomassen, M. n., Toland, A. E., Torres-Esquius, S. n., Tung, N. n., van Asperen, C. J., Vega, A. n., Viel, A. n., Vierstraete, J. n., Wappenschmidt, B. n., Weitzel, J. N., Wieme, G. n., Yoon, S. Y., Zorn, K. K., McGuffog, L. n., Parsons, M. T., Hamann, U. n., Greene, M. H., Kirk, J. A., Neuhausen, S. L., Rebbeck, T. R., Tischkowitz, M. n., Chenevix-Trench, G. n., Antoniou, A. C., Friedman, E. n., Ottini, L. n. 2020

  Abstract

  The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected.BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview.Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier.Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.

  View details for DOI 10.1001/jamaoncol.2020.2134

  View details for PubMedID 32614418

• Yield and Utility of Germline Testing Following Tumor Sequencing in Patients With Cancer. JAMA network open Lincoln, S. E., Nussbaum, R. L., Kurian, A. W., Nielsen, S. M., Das, K. n., Michalski, S. n., Yang, S. n., Ngo, N. n., Blanco, A. n., Esplin, E. D. 2020; 3 (10): e2019452

  Abstract

  Both germline genetic testing and tumor DNA sequencing are increasingly used in cancer care. The indications for testing and utility of these 2 tests differ, and guidelines recommend that germline analysis follow tumor sequencing in certain patients to determine whether particular variants are of somatic or germline origin. Broad clinical experience with such follow-up testing has not yet been thoroughly described.To examine the yield and utility of germline testing following tumor DNA sequencing in a large, diverse patient population.A retrospective cohort study examined germline testing through a laboratory supporting multiple academic and community clinics. Participants included 2023 patients with cancer who received germline testing and previously underwent tumor DNA sequencing. These patients received germline testing between January 5, 2015, and January 31, 2020, although most (81% of patients) received testing between January 2, 2018, and January 31, 2020.The prevalence of pathogenic germline variants (PGVs) was calculated by gene, cancer type, and age at diagnosis. Potential actionability of these findings was determined based on current management guidelines, precision therapy labels, and clinical trial eligibility criteria. Patient records were reviewed to determine whether germline follow-up testing would have been recommended by current guidelines.Among 2023 eligible patients, 1085 were female (53.6%), and the median age at cancer diagnosis was 56 (range, 0-92) years. Pathogenic germline variants were detected in 617 patients (30.5%; 95% CI, 28.5%-32.6%) and were prevalent across patient ages (1-85 years) and cancer types, including cancers known to be strongly associated with germline variance (eg, breast, colorectal) as well as others (eg, renal, lung, and bladder). Many patients (78%-82%) with PGVs met criteria for germline follow-up testing, and 8.1% of PGVs were missed by tumor sequencing. Among those with germline-positive findings, 69 patients (11.2%) had PGVs identified only after presenting with a second primary cancer that possibly could have been detected earlier or prevented given current gene-specific surveillance and risk-reduction recommendations.The findings of this study suggest that germline analysis following tumor sequencing often produces findings that may impact patient care by influencing systemic therapy choices, surgical decisions, additional cancer screening, and genetic counseling in families. Current guidelines and tumor testing approaches appear to capture many, but not all, of these germline findings, reinforcing the utility of both expanded germline follow-up testing as well as germline analysis independent of tumor sequencing in appropriate patients.

  View details for DOI 10.1001/jamanetworkopen.2020.19452

  View details for PubMedID 33026450

• Abstract IA50: Genetic testing, treatment and mortality after diagnosis of breast cancer or ovarian cancer: The SEER-GeneLINK Initiative Eleventh AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved Kurian, A. W. 2020

  View details for DOI 10.1158/1538-7755.DISP18-IA50

• Abstract 2033: Reducing cancer caregiver burden: A user-centered design approach for an mHealth app American Association for Cancer Research Annual Meeting Oakley-Girvan, I., Divi, V., Palesh, O., Daniels, J., Goldman Rosas, L., O'Brien, D., Davis, S. W., Kamal, A. H., Kurian, A. W., Longmire, M. R. 2020

  View details for DOI 10.1158/1538-7445.AM2020-2033

• Abstract P6-08-02: 21-gene recurrence score results according to germline pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2 and Lynch Syndrome genes San Antonio Breast Cancer Symposium Kurian, A. W., Abrahamse, P., Ward, K., Hamilton, A. S., Deapen, D., Katz, S. J. 2020

  View details for DOI 10.1158/1538-7445.SABCS19-P6-08-02

• Abstract P3-07-01: Breast cancer-specific mortality (BCSM) in patients age 50 years or younger with node-positive (N+) breast cancer (BC) treated based on the 21-gene assay in clinical practice San Antonio Breast Cancer Symposium Petkov, V., Kurian, A. W., Jakubowski, D. M., Shak, S. 2020

  View details for DOI 10.1158/1538-7445.SABCS19-P3-07-01

• Abstract P6-08-07: Polygenic breast cancer risk modification in carriers of high and intermediate risk gene mutations San Antonio Breast Cancer Symposium Gallagher, S., Hughes, E., Wagner, S., Tshiaba, P., Rosenthal, E., Roa, B. B., Kurian, A. W., Domchek, S., Garber, J., Lancaster, J. M., Weitzel, J., Gutin, A., Lanchbury, J. S., Robson, M. 2020

  View details for DOI 10.1158/1538-7445.SABCS19-P6-08-07

• Is Breast Cancer in Asian and Asian American Women a Different Disease? JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Gomez, S., Yao, S., Kushi, L. H., Kurian, A. W. 2019; 111 (12): 1243–44

  View details for DOI 10.1093/jnci/djz091

  View details for Web of Science ID 000509549100002

• Simulation Modeling to Extend Clinical Trials of Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Early Breast Cancer. JNCI cancer spectrum Jayasekera, J., Sparano, J. A., Gray, R., Isaacs, C., Kurian, A., O'Neill, S., Schechter, C. B., Mandelblatt, J. 2019; 3 (4): pkz062

  Abstract

  The Trial Assigning Individualized Options for Treatment (TAILORx) found chemotherapy could be omitted in many women with hormone receptor-positive, HER2-negative, node-negative breast cancer and 21-gene recurrence scores (RS) 11-25, but left unanswered questions. We used simulation modeling to fill these gaps.We simulated women eligible for TAILORx using joint distributions of patient and tumor characteristics and RS from TAILORx data; treatment effects by RS from other trials; and competing mortality from the Surveillance, Epidemiology, and End Results program database. The model simulations replicated TAILORx design, and then tested treatment effects on 9-year distant recurrence-free survival (DRFS) in 14 new scenarios: eight subgroups defined by age (≤50 and >50 years) and 21-gene RS (11-25/16-25/16-20/21-25); six different RS cut points among women ages 18-75 years (16-25, 16-20, 21-25, 26-30, 26-100); and 20-year follow-up. Mean hazard ratios SD, and DRFS rates are reported from 1000 simulations.The simulation results closely replicated TAILORx findings, with 75% of simulated trials showing noninferiority for chemotherapy omission. There was a mean DRFS hazard ratio of 1.79 (0.94) for endocrine vs chemoendocrine therapy among women ages 50 years and younger with RS 16-25; the DFRS rates were 91.6% (0.04) for endocrine and 94.8% (0.01) for chemoendocrine therapy. When treatment was randomly assigned among women ages 18-75 years with RS 26-30, the mean DRFS hazard ratio for endocrine vs chemoendocrine therapy was 1.60 (0.83). The conclusions were unchanged at 20-year follow-up.Our results confirmed a small benefit in chemotherapy among women aged 50 years and younger with RS 16-25. Simulation modeling is useful to extend clinical trials, indicate how uncertainty might affect results, and power decision tools to support broader practice discussions.

  View details for DOI 10.1093/jncics/pkz062

  View details for PubMedID 32337487

  View details for PubMedCentralID PMC7049983

• Mutations and the Importance of Genetic Testing ONCOLOGY-NEW YORK Kurian, A. W. 2019; 33 (10): 406-409

  View details for Web of Science ID 000608680100005

• Adherence to breast cancer treatment guidelines according to pathogenic variants in cancer susceptibility genes in a population-based cohort. Katz, S. J., Morrow, M., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.27_suppl.34

  View details for Web of Science ID 000518223100033

• Re: Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative Response JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Caswell-Jin, J. L., Kurian, A. W. 2019; 111 (8): 874

  View details for DOI 10.1093/jnci/djz029

  View details for Web of Science ID 000493066600021

• Primary care provider-reported involvement in breast cancer treatment decisions CANCER Wallner, L. P., Li, Y., McLeod, M., Gargaro, J., Kurian, A. W., Jagsi, R., Radhakrishnan, A., Hamilton, A. S., Ward, K. C., Hawley, S. T., Katz, S. J. 2019; 125 (11): 1815–22

  View details for DOI 10.1002/cncr.31998

  View details for Web of Science ID 000467473000011

• Preventive surgery after multiplex genetic panel testing (MGPT) Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Levonian, P., Hong, C., Mills, M., Ma, C., Lancaster, J. M., Brown, K., Kidd, J., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.1525

  View details for Web of Science ID 000487345804321

• Oncotype DX DCIS use and clinical utility: A SEER population-based study. Yuan, Y., Van Dyke, A., Kurian, A. W., Negoita, S., Petkov, V. I. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e12046

  View details for Web of Science ID 000487345800040

• Use, attitudes, and perceptions of tumor genomic testing: Survey of TAPUR physicians. Bruinooge, S. S., Dueck, A. C., Gray, S. W., Butler, N. L., White, C. B., Smith, M., Mangat, P. K., Kurian, A. W., Railey, E., Hawley, S. T., Schilsky, R. L. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.6531

  View details for Web of Science ID 000487345806085

• Prevalence and penetrance of breast cancer-associated mutations identified by multiple-gene sequencing in the Women's Health Initiative. Kurian, A. W., Hughes, E., Bernhisel, R., Larson, K., Caswell-Jin, J., Shadyab, A. H., Ochs-Balcom, H., Pan, K., Qi, L., Reding, K., Hartman, A., Lancaster, J. M., Tang, J. Y., Stefanick, M. L. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.1513

  View details for Web of Science ID 000487345804309

• Differences among Asian/Asian American, and Caucasian breast and gynecologic cancer patient reported survivorship needs, symptoms, and illness mindsets (N=220). Schapira, L., Hofmeister, E., Kurian, A. W., Zion, S., Shen, H., Torres, T., Berek, J. S., Palesh, O. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804287

• Breast cancer treatment according to pathogenic variants in cancer susceptibility genes in a population-based cohort. Kurian, A. W., Ward, K. C., Abrahamse, P., Hamilton, A. S., Deapen, D., Morrow, M., Katz, S. J. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.560

  View details for Web of Science ID 000487345803553

• Radiomics features to identify distinct subtypes of triple-negative breast cancers. Itakura, H., Ikeda, D. M., Okamoto, S., Chen, S., Rister, B., Gude, D., Mattonen, S. A., Alkim, E., Todderud, J., Schueler, E., Rubin, D., Sledge, G. W., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.3069

  View details for Web of Science ID 000487345805003

• Distribution of Global Health Measures From Routinely Collected PROMIS Surveys in Patients With Breast Cancer or Prostate Cancer CANCER Seneviratne, M. G., Bozkurt, S., Patel, M., Seto, T., Brooks, J. D., Blayney, D. W., Kurian, A. W., Hernandez-Boussard, T. 2019; 125 (6): 943–51

  View details for DOI 10.1002/cncr.31895

  View details for Web of Science ID 000461693200015

• Guidelines Do Not Proscribe Surgeons Performing Genetic Testing Reply JAMA SURGERY Katz, S. J., Morrow, M., Kurian, A. W. 2019; 154 (3): 269-270

  View details for DOI 10.1001/jamasurg.2018.4885

  View details for Web of Science ID 000461900900023

• Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk. JCO precision oncology Idos, G. E., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J. O., Kingham, K. E., Koff, R., Chun, N. M., Rowe-Teeter, C., Lebensohn, A. P., Levonian, P., Lowstuter, K., Partynski, K., Hong, C., Mills, M. A., Petrovchich, I., Ma, C. S., Hartman, A. R., Allen, B., Wenstrup, R. J., Lancaster, J. M., Brown, K., Kidd, J., Evans, B., Mukherjee, B., McDonnell, K. J., Ladabaum, U., Ford, J. M., Gruber, S. B. 2019; 3

  Abstract

  Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations.This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate).Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested.In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.

  View details for DOI 10.1200/PO.18.00217

  View details for PubMedID 34322651

  View details for PubMedCentralID PMC8260917

• Automatic Inference of BI-RADS Final Assessment Categories from Narrative Mammography Report Findings. Journal of biomedical informatics Banerjee, I., Bozkurt, S., Alkim, E., Sagreiya, H., Kurian, A. W., Rubin, D. L. 2019: 103137

  Abstract

  We propose an efficient natural language processing approach for inferring the BI-RADS final assessment categories by analyzing only the mammogram findings reported by the mammographer in narrative form. The proposed hybrid method integrates semantic term embedding with distributional semantics, producing a context-aware vector representation of unstructured mammography reports. A large corpus of unannotated mammography reports (300,000) was used to learn the context of the key-terms using a distributional semantics approach, and the trained model was applied to generate context-aware vector representations of the reports annotated with BI-RADS category(22,091). The vectorized reports were utilized to train a supervised classifier to derive the BI-RADS assessment class. Even though the majority of the proposed embedding pipeline is unsupervised, the classifier was able to recognize substantial semantic information for deriving the BI-RADS categorization not only on a holdout internal testset and also on an external validation set (1,900 reports). Our proposed method outperforms a recently published domain-specific rule-based system and could be relevant for evaluating concordance between radiologists. With minimal requirement for task specific customization, the proposed method can be easily transferable to a different domain to support large scale text mining or derivation of patient phenotype.

  View details for DOI 10.1016/j.jbi.2019.103137

  View details for PubMedID 30807833

• Using natural language processing to construct a metastatic breast cancer cohort from linked cancer registry and electronic medical records data. JAMIA open Ling, A. Y., Kurian, A. W., Caswell-Jin, J. L., Sledge, G. W., Shah, N. H., Tamang, S. R. 2019; 2 (4): 528–37

  Abstract

  Most population-based cancer databases lack information on metastatic recurrence. Electronic medical records (EMR) and cancer registries contain complementary information on cancer diagnosis, treatment and outcome, yet are rarely used synergistically. To construct a cohort of metastatic breast cancer (MBC) patients, we applied natural language processing techniques within a semisupervised machine learning framework to linked EMR-California Cancer Registry (CCR) data.We studied all female patients treated at Stanford Health Care with an incident breast cancer diagnosis from 2000 to 2014. Our database consisted of structured fields and unstructured free-text clinical notes from EMR, linked to CCR, a component of the Surveillance, Epidemiology and End Results Program (SEER). We identified de novo MBC patients from CCR and extracted information on distant recurrences from patient notes in EMR. Furthermore, we trained a regularized logistic regression model for recurrent MBC classification and evaluated its performance on a gold standard set of 146 patients.There were 11 459 breast cancer patients in total and the median follow-up time was 96.3 months. We identified 1886 MBC patients, 512 (27.1%) of whom were de novo MBC patients and 1374 (72.9%) were recurrent MBC patients. Our final MBC classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.917, with sensitivity 0.861, specificity 0.878, and accuracy 0.870.To enable population-based research on MBC, we developed a framework for retrospective case detection combining EMR and CCR data. Our classifier achieved good AUC, sensitivity, and specificity without expert-labeled examples.

  View details for DOI 10.1093/jamiaopen/ooz040

  View details for PubMedID 32025650

  View details for PubMedCentralID PMC6994019

• Can precision medicine help achieve the goal of reducing care when the risks exceed the benefits? Personalized Medicine Phillips, K. A., Marshall, D. A., Kurian, A. W. 2019

  View details for DOI 10.2217/pme-2019-0045

• Decision Making About Genetic Testing Among Women With a Personal and Family History of Breast Cancer. Journal of oncology practice Scott, D. n., Friedman, S. n., Telli, M. L., Kurian, A. W. 2019: JOP1900221

  Abstract

  To understand genetic testing use and decision making among patients with high genetic risk.A survey of breast cancer survivors was administered online by a hereditary cancer nonprofit organization, Facing Our Risk of Cancer Empowered, from October 2017 to March 2018.Of 1,322 respondents, 46% had breast cancer at age < 45 years, 61% had a first-degree relative with cancer, and 84% underwent genetic testing, of whom 56% had a risk-associated pathogenic variant. Most (86%; 95% CI, 84% to 88%) tested respondents were very satisfied with their testing decision, versus 34% (95% CI, 27% to 41%) of untested respondents. Factors that encouraged testing included relatives' cancer risk (75%; 95% CI, 73% to 78%), clinicians' recommendations (68%; 95% CI, 66% to 71%), and potential treatment implications (67%; 95% CI, 64% to 69%). Factors that discouraged testing included insurance concerns (14%; 95% CI, 12% to 16%), cost (14%; 95% CI, 12% to 16%), and discrimination (9%; 95% CI, 7% to 11%). Thirty-nine percent (95% CI, 36% to 41%) recalled hearing from a clinician that genetic discrimination is illegal. Respondents often recalled clinicians informing them about inheritance patterns (65%; 95% CI, 62% to 67%), surgical implications (65%; 95% CI, 63% to 68%), and other cancer risks (66%; 95% CI, 63% to 68%) but less often that results could have potential implications for clinical trial eligibility (38%; 95% CI, 36% to 42%) or targeted therapies (14%; 95% CI, 12% to 16%). Patients who had genetic counseling were twice as likely to recall clinicians informing them about all queried topics. Results did not vary by diagnosis year.Among patients with high genetic risk, clinicians' recommendations, potential treatment implications, and protections against discrimination were motivating factors to undergo genetic testing, but fewer than half recalled clinicians providing all this information, and this did not improve over time. Clinicians influence testing decisions and should inform patients about legal protections and treatment implications.

  View details for DOI 10.1200/JOP.19.00221

  View details for PubMedID 31613719

• Modeling reductions in absolute cancer mortality from diagnosing cancers before metastasis, 2006-2015 Clarke, C. A., Hubbell, E., Hartman, A., Colditz, G., Kurian, A. W., Gomez, S. L. 2019: S296–S297
• Clinical and pathological features of breast cancer among men and women with ATM and CDH1 mutations American Society of Breast Surgeons Annual Meeting Tsang, A., Kingham, K., Kurian, A. W. 2019: 69–70
• Genomic landscape of ductal carcinoma in situ and association with progression. Breast cancer research and treatment Lin, C. Y., Vennam, S. n., Purington, N. n., Lin, E. n., Varma, S. n., Han, S. n., Desa, M. n., Seto, T. n., Wang, N. J., Stehr, H. n., Troxell, M. L., Kurian, A. W., West, R. B. 2019

  Abstract

  The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is overdiagnosed and overtreated. Therefore, there is an unmet clinical need to better predict the risk of progression among DCIS patients. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS.Targeted exon sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or subsequent invasive breast cancer (IBC) (DCIS + IBC group), and 65 from cases with no IBC development over a median follow-up of 13 years (DCIS-only group). Copy number alterations in chromosome 1q32, 8q24, and 11q13 were analyzed using fluorescence in situ hybridization (FISH). Multivariable logistic regression models were fit to the outcome of DCIS progression to IBC as functions of demographic and clinical features.We observed recurrent variants of known IBC-related mutations, and the most commonly mutated genes in DCIS were PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA kinase domain mutations and progression (Odds Ratio [OR] 10.2, p < 0.05). Copy number variations in 1q32 and 8q24 were associated with progression (OR 9.3 and 46, respectively; both p < 0.05).PIK3CA kinase domain mutations and the absence of copy number gains in DCIS are protective against progression to IBC. These results may guide efforts to distinguish low-risk from high-risk DCIS.

  View details for DOI 10.1007/s10549-019-05401-x

  View details for PubMedID 31420779

• Chromatin Remodeling in Response to BRCA2-Crisis. Cell reports Gruber, J. J., Chen, J. n., Geller, B. n., Jäger, N. n., Lipchik, A. M., Wang, G. n., Kurian, A. W., Ford, J. M., Snyder, M. P. 2019; 28 (8): 2182–93.e6

  Abstract

  Individuals with a single functional copy of the BRCA2 tumor suppressor have elevated risks for breast, ovarian, and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to BRCA2 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function ("BRCA2-crisis"), which may contribute to disease. Here, we establish an in vitro model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These chromatin alterations are reflected in transcriptional profiles of pre-malignant tissues from BRCA2 carriers and, therefore, may reflect natural steps in human disease. By modeling BRCA2-crisis in vitro, we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.

  View details for DOI 10.1016/j.celrep.2019.07.057

  View details for PubMedID 31433991

• Magnitude of reduction in risk of second contralateral breast cancer with bilateral mastectomy in patients with breast cancer: Data from California, 1998 through 2015. Cancer Kurian, A. W., Canchola, A. J., Ma, C. S., Clarke, C. A., Gomez, S. L. 2019

  Abstract

  Increasingly, patients with breast cancer undergo bilateral mastectomy (BLM). To the authors' knowledge, the magnitude of benefit is unknown.The authors used data from the Surveillance, Epidemiology, and End Results (SEER) program regarding all women diagnosed with American Joint Committee on Cancer stage 0 to stage III unilateral breast cancer in California from 1998 through 2015 and treated with BLM versus breast-conserving therapy including surgery and radiotherapy (BCT) or unilateral mastectomy (ULM). The authors measured relative risks of second contralateral breast cancer (CBC) and breast cancer death using Fine and Gray multivariable regression modeling adjusted for the competing risk of death and death from another cause, respectively, and potential confounding factors. Absolute excess risk of CBC was measured as the observed minus expected number of breast cancers in the general population divided by 10,000 person-years at risk.Among 245,418 patients with a median follow-up of 6.7 years, 7784 patients (3.2%) developed CBC. Relative risks were lower after BLM (hazard ratio [HR], 0.10; 95% CI, 0.07-0.14) and higher after ULM (HR, 1.07; 95% CI, 1.02-1.13) versus BCT. Absolute excess risks were higher after BCT and ULM (5.0 and 13.6 more cases, respectively) compared with BLM (28.6 fewer cases). BLM reduced risk more among older women (38.0 fewer cases for women aged ≥50 years vs 17.9 fewer cases among women aged <50 years) but provided similar risk reduction across categories of tumor grade and tumor hormone receptor status. Compared with BCT, the risk of breast cancer death was equivalent after BLM (HR, 1.03; 95% CI, 0.96-1.11) and higher after ULM (HR, 1.21; 95% CI, 1.17-1.25).BLM may reduce second breast cancer risk by 34 to 43 cases per 10,000 person-years compared with other surgical procedures, but is not associated with a lower risk of death. Second breast cancers are rare, and their reduction should be weighed against the harms associated with BLM.

  View details for DOI 10.1002/cncr.32618

  View details for PubMedID 31750934

• Natural Language Processing Approaches to Detect the Timeline of Metastatic Recurrence of Breast Cancer. JCO clinical cancer informatics Banerjee, I. n., Bozkurt, S. n., Caswell-Jin, J. L., Kurian, A. W., Rubin, D. L. 2019; 3: 1–12

  Abstract

  Electronic medical records (EMRs) and population-based cancer registries contain information on cancer outcomes and treatment, yet rarely capture information on the timing of metastatic cancer recurrence, which is essential to understand cancer survival outcomes. We developed a natural language processing (NLP) system to identify patient-specific timelines of metastatic breast cancer recurrence.We used the OncoSHARE database, which includes merged data from the California Cancer Registry and EMRs of 8,956 women diagnosed with breast cancer in 2000 to 2018. We curated a comprehensive vocabulary by interviewing expert clinicians and processing radiology and pathology reports and progress notes. We developed and evaluated the following two distinct NLP approaches to analyze free-text notes: a traditional rule-based model, using rules for metastatic detection from the literature and curated by domain experts; and a contemporary neural network model. For each 3-month period (quarter) from 2000 to 2018, we applied both models to infer recurrence status for that quarter. We trained the NLP models using 894 randomly selected patient records that were manually reviewed by clinical experts and evaluated model performance using 179 hold-out patients (20%) as a test set.The median follow-up time was 19 quarters (5 years) for the training set and 15 quarters (4 years) for the test set. The neural network model predicted the timing of distant metastatic recurrence with a sensitivity of 0.83 and specificity of 0.73, outperforming the rule-based model, which had a specificity of 0.35 and sensitivity of 0.88 (P < .001).We developed an NLP method that enables identification of the occurrence and timing of metastatic breast cancer recurrence from EMRs. This approach may be adaptable to other cancer sites and could help to unlock the potential of EMRs for research on real-world cancer outcomes.

  View details for DOI 10.1200/CCI.19.00034

  View details for PubMedID 31584836

• Patient-clinician interactions and disparities in breast cancer care: the equality in breast cancer care study. Journal of cancer survivorship : research and practice Gonzales, F. A., Sangaramoorthy, M. n., Dwyer, L. A., Shariff-Marco, S. n., Allen, A. M., Kurian, A. W., Yang, J. n., Langer, M. M., Allen, L. n., Reeve, B. B., Taplin, S. H., Gomez, S. L. 2019

  Abstract

  To examine whether interpersonal aspects of patient-clinician interactions, such as patient-perceived medical discrimination, clinician mistrust, and treatment decision-making contribute to racial/ethnic/educational disparities in breast cancer care.A telephone interview was administered to 542 Asian/Pacific Islander (API), Black, Hispanic, and White women identified through the Greater Bay Area Cancer Registry, ages 20 and older diagnosed with a first primary invasive breast cancer. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated from logistic regression models that assessed associations between race/ethnicity/education, medical discrimination, clinician mistrust, and treatment decision-making with concordance to breast cancer treatment guidelines (guideline-concordant treatment) and perceived quality of care (pQoC).Approximately three-quarters of women received treatment that was guideline-concordant (76.6%) and reported that their breast cancer care was excellent (72.1%). Non-college-educated Black women had lower odds of guideline-concordant care (aOR (CI) = 0.29 (0.12-0.67)) vs. college-educated White women. Odds of excellent pQoC were lower among the following: college-educated Hispanic women (aOR (CI) = 0.09 (0.02-0.47)) and API women regardless of education (aORs ≤ 0.50) vs. college-educated White women, women reporting low and moderate levels of discrimination (aORs ≤ 0.44) vs. none, and women reporting any clinician mistrust (aOR (CI) = 0.50 (0.29-0.88)) vs. none. Disparities in guideline-concordant care and pQoC persisted after controlling for medical discrimination, clinician mistrust, and decision-making.Interpersonal aspects of the patient-clinician interaction had an impact on pQoC but not receipt of guideline-concordant treatment and did not explain disparities in either outcome.Although breast cancer survivors' interpersonal interactions with clinicians did not influence receipt of appropriate treatment, intervention strategies to improve patient-clinician relations may help attenuate disparities in survivors' pQoC.

  View details for DOI 10.1007/s11764-019-00820-7

  View details for PubMedID 31646462

• Comparative effectiveness of first-line nab-paclitaxel versus paclitaxel monotherapy in triple-negative breast cancer. Journal of comparative effectiveness research Luhn, P. n., Chui, S. Y., Hsieh, A. F., Yi, J. n., Mecke, A. n., Bajaj, P. S., Hasnain, W. n., Falgas, A. n., Ton, T. G., Kurian, A. W. 2019

  Abstract

  Aim: This observational study evaluated the effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line (1L) treatment for metastatic triple-negative breast cancer (mTNBC). Materials & methods: 200 patients from the US Flatiron Health electronic health record-derived database (mTNBC diagnosis, January 2011-October 2016) who received 1L nab-paclitaxel (n = 105) or paclitaxel (n = 95) monotherapy were included. Overall survival and time to next treatment were evaluated. Results: The adjusted overall survival hazard ratio was 0.98 (95% CI: 0.67-1.44), indicating a similar risk of death between groups. Adjusted time to next treatment hazard ratio was 0.89 (95% confidence interval: 0.62-1.29). Conclusion: Nab-paclitaxel and paclitaxel monotherapy showed similar efficacy, suggesting their interchangeability as 1L treatments for mTNBC.

  View details for DOI 10.2217/cer-2019-0077

  View details for PubMedID 31394922

• Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry. EBioMedicine Yang, Y. n., Shu, X. n., Shu, X. O., Bolla, M. K., Kweon, S. S., Cai, Q. n., Michailidou, K. n., Wang, Q. n., Dennis, J. n., Park, B. n., Matsuo, K. n., Kwong, A. n., Park, S. K., Wu, A. H., Teo, S. H., Iwasaki, M. n., Choi, J. Y., Li, J. n., Hartman, M. n., Shen, C. Y., Muir, K. n., Lophatananon, A. n., Li, B. n., Wen, W. n., Gao, Y. T., Xiang, Y. B., Aronson, K. J., Spinell, J. J., Gago-Dominguez, M. n., John, E. M., Kurian, A. W., Chang-Claude, J. n., Chen, S. T., Dörk, T. n., Evans, D. G., Schmidt, M. K., Shin, M. H., Giles, G. G., Milne, R. L., Simard, J. n., Kubo, M. n., Kraft, P. n., Kang, D. n., Easton, D. F., Zheng, W. n., Long, J. n. 2019

  Abstract

  We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS.Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

  View details for DOI 10.1016/j.ebiom.2019.09.006

  View details for PubMedID 31629678

• Uptake of the 21-Gene Assay Among Women With Node-Positive, Hormone Receptor-Positive Breast Cancer. Journal of the National Comprehensive Cancer Network : JNCCN Roberts, M. C., Kurian, A. W., Petkov, V. I. 2019; 17 (6): 662–68

  Abstract

  This study assessed uptake of the Oncotype DX 21-gene assay over time and characterized which sociodemographic and clinical factors are associated with test uptake among women with lymph node-positive (LN+), hormone receptor-positive, HER2-negative breast cancer.Invasive breast cancer cases diagnosed in 2010 through 2013 were included from a SEER database linked to 21-gene assay results performed at Genomic Health's Clinical Laboratory. Factors associated with 21-gene assay uptake were identified using a multivariable logistic regression model.Uptake of the 21-gene assay increased over time and differed by race, socioeconomic status (SES), and age. In the multivariable model, when clinical and SES variables were controlled for, racial differences in test uptake were no longer observed. Private insurance status was associated with higher odds of 21-gene assay uptake (Medicaid vs private insurance: adjusted odds ratio, 0.86; P=.02), and high area-level SES was associated with an increased odds of uptake (quintile 5 vs 1: adjusted odds ratio, 1.6; P<.001). Demographic factors such as age and marital status influenced test uptake, and use varied greatly by geographic region. Uptake of the 21-gene assay increased over time and preceded the assay's inclusion in the NCCN Guidelines for LN+ breast cancer. Differences in uptake by race, SES, and age have persisted over time. However, when clinical and SES variables were controlled for, racial differences in assay uptake were no longer observed. Socioeconomic variables, such as health insurance type and area-level SES, were associated with assay uptake.Future research should continue to document practice patterns related to the 21-gene assay. Given variation in testing associated with area-level SES, insurance coverage, and geographic region, interventions to understand and reduce differential uptake are needed to ensure equitable access to this genomic test.

  View details for DOI 10.6004/jnccn.2018.7266

  View details for PubMedID 31200352

• Rising rates of bilateral mastectomy with reconstruction following neoadjuvant chemotherapy INTERNATIONAL JOURNAL OF CANCER Pollom, E. L., Qian, Y., Chin, A. L., Dirbas, F. M., Asch, S. M., Kurian, A. W., Horst, K. C., Tsai, C. 2018; 143 (12): 3262–72

  View details for DOI 10.1002/ijc.31747

  View details for Web of Science ID 000451115900020

• Cancer Risk Estimates for Study of Multiple-Gene Testing After Diagnosis of Breast Cancer Reply JAMA ONCOLOGY Kurian, A. W., Katz, S. J. 2018; 4 (12): 1788

  View details for DOI 10.1001/jamaoncol.2018.4959

  View details for Web of Science ID 000453212800036

• Can We Use Survival Data from Cancer Registries to Learn about Disease Recurrence? The Case of Breast Cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Mariotto, A. B., Zou, Z., Zhang, F., Howlader, N., Kurian, A. W., Etzioni, R. 2018; 27 (11): 1332-1341

  View details for DOI 10.1158/1055-9965.EPI-17-1129

  View details for Web of Science ID 000448896500013

• Pathogenic Variants in Less Familiar Cancer Susceptibility Genes: What Happens After Genetic Testing? JCO precision oncology Hall, E. T., Parikh, D., Caswell-Jin, J. L., Gupta, T., Mills, M. A., Kingham, K. E., Koff, R., Ford, J. M., Kurian, A. W. 2018; 2: 1-10

  Abstract

  As genetic testing expands, patients are increasingly found to carry pathogenic variants in cancer susceptibility genes that are less familiar to most clinicians, specifically genes other than those causing hereditary breast ovarian cancer syndrome (BRCA1 and BRCA2) and Lynch syndrome. Little is known about the subsequent behaviors of such patients in terms of managing cancer risks and informing relatives.All adult patients who were counseled and tested at the Stanford Cancer Genetics Clinic from January 2013 to July 2015 and had a pathogenic variant in a non-BRCA1/2, non-Lynch syndrome gene were invited to participate in a telephone interview about adherence to risk-reducing recommendations, genetic testing by relatives, and new cancer incidence.Fifty-seven (40%) of 142 eligible patients were successfully contacted, and all 57 patients participated; median follow-up was 677 days (range, 247 to 1,401 days). Most patients (82%; 95% CI, 70% to 90%) recalled that a risk-reducing intervention (screening, medication, or surgery) was recommended, and most patients (85%; 95% CI, 72% to 93%) adhered to the recommendation. Nearly all patients (91%; 95% CI, 81% to 97%) shared results with relatives, and most patients (78%; 95% CI, 64% to 88%) reported that a relative was subsequently tested. During the follow-up period, 9% of patients (95% CI, 3% to 19%) developed second cancers, and in 14% of patients (95% CI, 7% to 26%), a first-degree relative developed cancer, some of which were detected by recommended screening.Patients with a pathogenic variant in a less familiar cancer susceptibility gene report high adherence to risk-reducing interventions. Furthermore, in the 57 carriers and subsequently tested relatives with two years of follow-up, a total of three cancers (one in a proband and two in relatives) were detected through interventions recommended on the basis of the pathogenic variant. These results suggest a potential benefit of genetic counseling and testing for pathogenic variants in less familiar genes.

  View details for DOI 10.1200/PO.18.00167

  View details for PubMedID 35135157

• Knowledge Regarding and Patterns of Genetic Testing in Patients Newly Diagnosed With Breast Cancer Participating in the iCanDecide Trial. Cancer Gornick, M. C., Kurian, A. W., An, L. C., Fagerlin, A., Jagsi, R., Katz, S. J., Hawley, S. T. 2018

  Abstract

  The current study reports rates of knowledge regarding the probability of a BRCA1 and/or S pathogenic variant and genetic testing in patients with breast cancer, collected as part of a randomized controlled trial of a tailored, comprehensive, and interactive decision tool (iCanDecide).A total of 537 patients newly diagnosed with early-stage breast cancer were enrolled at the time of their first visit in 22 surgical practices, and were surveyed 5 weeks (496 patients; Response Rate [RR], 92%) after enrollment after treatment decision making. Primary outcomes included knowledge regarding the probability of carrying a BRCA1 and/or BRCA2 pathogenic variant and genetic testing after diagnosis.Overall knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant was low (29.8%). Significantly more patients in the intervention group compared with the control group had knowledge regarding the probability of a BRCA1 and/or BRCA2 pathogenic variant (35.8% vs 24.4%; P <.006). In multivariable logistic regression, the intervention arm remained significantly associated with knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant (odds ratio, 1.79; 95% confidence interval, 1.18-2.70).The results of the current study suggest that although knowledge concerning the probability of having a BRCA1 and/or BRCA2 pathogenic variant remains low in this patient population, the interactive decision tool improved rates compared with a static Web site. As interest in genetic testing continues to rise, so will the need to integrate tools into the treatment decision process to improve informed decision making.

  View details for DOI 10.1002/cncr.31731

  View details for PubMedID 30289174

• A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging. Cell Keren, L., Bosse, M., Marquez, D., Angoshtari, R., Jain, S., Varma, S., Yang, S., Kurian, A., Van Valen, D., West, R., Bendall, S. C., Angelo, M. 2018; 174 (6): 1373

  Abstract

  The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology.

  View details for PubMedID 30193111

• From the Past to the Present: Insurer Coverage Frameworks for Next-Generation Tumor Sequencing. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Trosman, J. R., Weldon, C. B., Gradishar, W. J., Benson, A. B., Cristofanilli, M., Kurian, A. W., Ford, J. M., Balch, A., Watkins, J., Phillips, K. A. 2018; 21 (9): 1062-1068

  Abstract

  Next-generation sequencing promises major advancements in precision medicine but faces considerable challenges with insurance coverage. These challenges are especially important to address in oncology in which next-generation tumor sequencing (NGTS) holds a particular promise, guiding the use of life-saving or life-prolonging therapies. Payers' coverage decision making on NGTS is challenging because this revolutionary technology pushes the very boundaries of the underlying framework used in coverage decisions. Some experts have called for the adaptation of the coverage framework to make it better equipped for assessing NGTS. Medicare's recent decision to cover NGTS makes this topic particularly urgent to examine. In this article, we discussed the previously proposed approaches for adaptation of the NGTS coverage framework, highlighted their innovations, and outlined remaining gaps in their ability to assess the features of NGTS. We then compared the three approaches with Medicare's national coverage determination for NGTS and discussed its implications for US private payers as well as for other technologies and clinical areas. We focused on US payers because analyses of coverage approaches and policies in the large and complex US health care system may inform similar efforts in other countries. We concluded that further adaptation of the coverage framework will facilitate a better suited assessment of NGTS and future genomics innovations.

  View details for DOI 10.1016/j.jval.2018.06.011

  View details for PubMedID 30224110

• Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence following Radiotherapy in Immunosuppressed Patients CANCER RESEARCH Rafat, M., Aguilera, T. A., Vilalta, M., Bronsart, L. L., Soto, L. A., von Eyben, R., Golla, M. A., Ahrari, Y., Melemenidis, S., Afghahi, A., Jenkins, M. J., Kurian, A. W., Horst, K. C., Giaccia, A. J., Graves, E. E. 2018; 78 (15): 4241-4252

  View details for DOI 10.1158/0008-5472.CAN-17-3623

  View details for Web of Science ID 000440817300013

• Intratumoral Spatial Heterogeneity at Perfusion MR Imaging Predicts Recurrence-free Survival in Locally Advanced Breast Cancer Treated with Neoadjuvant Chemotherapy RADIOLOGY Wu, J., Cao, G., Sun, X., Lee, J., Rubin, D. L., Napel, S., Kurian, A. W., Daniel, B. L., Li, R. 2018; 288 (1): 26–35

  View details for DOI 10.1148/radiol.2018172462

  View details for Web of Science ID 000441805800008

• Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer CLINICAL CANCER RESEARCH Afghahi, A., Purington, N., Han, S. S., Desai, M., Pierson, E., Mathur, M. B., Seto, T., Thompson, C. A., Rigdon, J., Telli, M. L., Badve, S. S., Curtis, C. N., West, R. B., Horst, K., Gomez, S. L., Ford, J. M., Sledge, G. W., Kurian, A. W. 2018; 24 (12): 2851–58

  View details for DOI 10.1158/1078-0432.CCR-17-1323

  View details for Web of Science ID 000435462700016

• Promoting colorectal cancer (CRC) screening after multiplex genetic testing and genetic counseling Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Kidd, J., Evans, B., Brown, K., Mills, M., Ma, C., Hong, C., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.1582

  View details for Web of Science ID 000442916001199

• Unmet need for clinician engagement about financial toxicity after diagnosis of breast cancer. Jagsi, R., Ward, K. C., Abrahamse, P., Wallner, L. P., Kurian, A. W., Hamilton, A. S., Katz, S. J., Hawley, S. T. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.10080

  View details for Web of Science ID 000442916003445

• Promoting breast cancer screening after multiplex genetic panel testing (MGPT) and genetic counseling Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Kidd, J., Evans, B., Brown, K., Mills, M., Ma, C., Hong, C., McDonnell, K. J., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.1581

  View details for Web of Science ID 000442916001198

• Genetic testing and results in population-based breast cancer patients and ovarian cancer patients Kurian, A. W., Ward, K. C., Howlader, N., Deapen, D., Hamilton, A. S., Mariotto, A., Miller, D., Katz, S. J., Penberthy, L. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.1578

  View details for Web of Science ID 000442916001195

• Computing the cost of care per day of breast cancer survivor care. Blayney, D. W., Lindquist, C., Seto, T., Nhat Minh Hoang, Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.7_suppl.10

  View details for Web of Science ID 000443285600010

• Association of Germline Genetic Test Type and Results With Patient Cancer Worry After Diagnosis of Breast Cancer. JCO precision oncology Katz, S. J., Ward, K. C., Hamilton, A. S., Abrahamse, P. n., Hawley, S. T., Kurian, A. W. 2018; 2018

  Abstract

  There are concerns that multigene panel testing compared with BRCA1/ 2-only testing after diagnosis of breast cancer may lead to unnecessary patient worry about cancer because of more ambiguous results.Patients with breast cancer diagnosed from 2013 to 2015 and accrued from SEER registries in Georgia and Los Angeles were surveyed (n = 5,080; response rate, 70%), and responses were merged with SEER data and germline genetic testing and results. We examined patient reports of cancer worry by test type and results in 1,063 women who linked to a genetic test and reported undergoing testing.More than half of the sample (n = 640; 60.2%) received BRCA1/2-only testing versus 423 patients (39.8%) who had a multigene panel. A minority of tested patients reported substantial cancer worry after treatment: 11.1% (n = 130) reported higher impact of cancer worry, and 15.1% (n = 162) reported a high frequency of cancer worry (worrying often or almost always) in the past month. Impact of cancer worry did not substantively differ by test type, test result outcomes, or clinical or treatment factors. The odds ratio for higher impact of cancer worry was 0.81 (95% CI, 0.51 to 1.28) for multigene versus BRCA1/2-only testing. In a separate model, the odds ratios were 1.21 (95% CI, 0.54 to 2.68) and 0.90 (95% CI, 0.50 to 1.62) for pathogenic variant and variant of uncertain significance, respectively, versus a negative test (the reference group).Compared with BRCA1/2 testing alone, multigene panel testing was not associated with increased cancer worry after diagnosis of breast cancer.

  View details for PubMedID 30656245

• Comparative effectiveness of nab-paclitaxel versus paclitaxel monotherapy as first-line treatment of metastatic triple-negative breast cancer in US clinical practice European Society of Medical Oncology Annual Meeting Luhn, P., Chui, S., Hsieh, A., Yi, J., Mecke, A., Bajaj, P., Hasnain, W., Falgas, A., Ton, T. G., Kurian, A. W. 2018: 101
• Molecular receptor profiles in male mutation carriers with breast cancer American Society of Breast Surgeons Annual Meeting Wapnir, I. L., Kingham, K. E., Mills, M., Ford, J. M., Kurian, A. W. 2018: 112–13
• Outcomes in patients with metastatic triple-negative breast cancer treated in second line in the US real-world setting San Antonio Breast Cancer Symposium Luhn, P., O'Hear, C., Ton, T. G., Hsieh, A., Yi, J., Chang, C. W., Funke, R., Kurian, A. W. 2018
• Screening for founder and recurrent BRCA mutations in Hong Kong and US Chinese populations Hong Kong Medical Journal Kwong, A., Shin, V. Y., Ma, E. S., Chan, C. T., Ford, J. M., Kurian, A. W., Tai, E. 2018; 24: 4-6
• Change in survival in metastatic breast cancer with treatment advances: meta-analysis and systematic review JNCI Cancer Spectrum Caswell-Jin, J. L., Plevritis, S. K., Tian, L., Cadham, C. J., Xu, C., Stout, N. K., Sledge, G. W., Mandelblatt, J. S., Kurian, A. W. 2018; 2 (4)

  View details for DOI 10.1093/jncics/pky062

• Unmet Need for Clinician Engagement Regarding Financial Toxicity After Diagnosis of Breast Cancer. Cancer Jagsi, R. n., Ward, K. C., Abrahamse, P. H., Wallner, L. P., Kurian, A. W., Hamilton, A. S., Katz, S. J., Hawley, S. T. 2018

  Abstract

  Little is known regarding whether growing awareness of the financial toxicity of a cancer diagnosis and its treatment has increased clinician engagement or changed the needs of current patients.The authors surveyed patients with early-stage breast cancer who were identified through population-based sampling from 2 Surveillance, Epidemiology, and End Results (SEER) regions and their physicians. The authors described responses from approximately 73% of surgeons (370 surgeons), 61% of medical oncologists (306 medical oncologists), 67% of radiation oncologists (169 radiation oncologists), and 68% of patients (2502 patients).Approximately one-half (50.9%) of responding medical oncologists reported that someone in their practice often or always discusses financial burden with patients, as did 15.6% of surgeons and 43.2% of radiation oncologists. Patients indicated that financial toxicity remains common: 21.5% of white patients and 22.5% of Asian patients had to cut down spending on food, as did 45.2% of black and 35.8% of Latina patients. Many patients desired to talk to providers about the financial impact of cancer (15.2% of whites, 31.1% of blacks, 30.3% of Latinas, and 25.4% of Asians). Unmet patient needs for engagement with physicians about financial concerns were common. Of 945 women who worried about finances, 679 (72.8%) indicated that physicians and their staff did not help. Of 523 women who desired to talk to providers regarding the impact of breast cancer on employment or finances, 283 (55.4%) reported no relevant discussion.Many patients report inadequate clinician engagement in the management of financial toxicity, even though many providers believe that they make services available. Clinician assessment and communication regarding financial toxicity must improve; cure at the cost of financial ruin is unacceptable. Cancer 2018;000:000-000. © 2018 American Cancer Society.

  View details for PubMedID 30033631

• Association of Attending Surgeon With Variation in the Receipt of Genetic Testing After Diagnosis of Breast Cancer. JAMA surgery Katz, S. J., Bondarenko, I. n., Ward, K. C., Hamilton, A. S., Morrow, M. n., Kurian, A. W., Hofer, T. P. 2018

  Abstract

  Genetic testing after diagnosis of breast cancer is common, but little is known about the influence of the surgeon on the variation in testing.To quantify and explain the association of attending surgeon with rates of genetic testing after diagnosis of breast cancer.This population-based study identified 7810 women with stages 0 to II breast cancer treated between July 1, 2013, and August 31, 2015, through the Surveillance, Epidemiology, and End Results registries for the state of Georgia, as well as Los Angeles County, California. Surveys were sent approximately 2 months after surgery. Also surveyed were 488 attending surgeons identified by the patients.The study examined the association of surgeon with variation in the receipt of genetic testing using information from patient and surgeon surveys merged to Surveillance, Epidemiology, and End Results and genetic testing data obtained from 4 laboratories.In total, 5080 women (69.6%) of 7303 who were eligible (mean [SD] age, 61.4 [0.8] years) and 377 surgeons (77.3%) of 488 (mean [SD] age, 53.8 [10.7] years) responded to the survey. Approximately one-third (34.5% [1350 of 3910] of patients had an elevated risk of mutation carriage, and 27.0% (1056 of 3910) overall had genetic testing. Surgeons had practiced a mean (SE) of 20.9 (0.6) years, and 28.9% (107 of 370) treated more than 50 cases of new breast cancer per year. The odds of a patient receiving genetic testing increased more than 2-fold (odds ratio, 2.48; 95% CI, 1.85-3.31) if she saw a surgeon with an approach 1 SD above that of a surgeon with the mean test rate. Approximately one-third (34.1%) of the surgeon variation was explained by patient volume and surgeon attitudes about genetic testing and counseling. If a patient with higher pretest risk saw a surgeon at the 5th percentile of the surgeon distribution, she would have a 26.3% (95% CI, 21.9%-31.2%) probability of testing compared with 72.3% (95% CI, 66.7%-77.2%) if she saw a surgeon at the 95th percentile.In this study, the attending surgeon was associated with the receipt of genetic testing after a breast cancer diagnosis. Variation in surgeon attitudes about genetic testing and counseling may explain a substantial amount of this association.

  View details for PubMedID 29971344

• Common Model Inputs Used in CISNET Collaborative Breast Cancer Modeling. Medical decision making : an international journal of the Society for Medical Decision Making Mandelblatt, J. S., Near, A. M., Miglioretti, D. L., Munoz, D. n., Sprague, B. L., Trentham-Dietz, A. n., Gangnon, R. n., Kurian, A. W., Weedon-Fekjaer, H. n., Cronin, K. A., Plevritis, S. K. 2018; 38 (1_suppl): 9S–23S

  Abstract

  Since their inception in 2000, the Cancer Intervention and Surveillance Network (CISNET) breast cancer models have collaborated to use a nationally representative core of common input parameters to represent key components of breast cancer control in each model. Employment of common inputs permits greater ability to compare model output than when each model begins with different input parameters. The use of common inputs also enhances inferences about the results, and provides a range of reasonable results based on variations in model structure, assumptions, and methods of use of the input values. The common input data are updated for each analysis to ensure that they reflect the most current practice and knowledge about breast cancer. The common core of parameters includes population rates of births and deaths; age- and cohort-specific temporal rates of breast cancer incidence in the absence of screening and treatment; effects of risk factors on incidence trends; dissemination of plain film and digital mammography; screening test performance characteristics; stage or size distribution of screen-, interval-, and clinically- detected tumors by age; the joint distribution of ER/HER2 by age and stage; survival in the absence of screening and treatment by stage and molecular subtype; age-, stage-, and molecular subtype-specific therapy; dissemination and effectiveness of therapies over time; and competing non-breast cancer mortality.In this paper, we summarize the methods and results for the common input values presently used in the CISNET breast cancer models, note assumptions made because of unobservable phenomena and/or unavailable data, and highlight plans for the development of future parameters.These data are intended to enhance the transparency of the breast CISNET models.

  View details for PubMedID 29554466

• Rapid detection ofBRCA1/2recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels. Oncotarget Kwong, A. n., Ho, J. C., Shin, V. Y., Kurian, A. W., Tai, E. n., Esserman, L. J., Weitzel, J. N., Lin, P. H., Field, M. n., Domchek, S. M., Lo, J. n., Ngan, H. Y., Ma, E. S., Chan, T. L., Ford, J. M. 2018; 9 (8): 7832–43

  Abstract

  BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 ChineseBRCA1/2mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS).BRCAmutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novelBRCA2mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC.

  View details for PubMedID 29487695

• Patient communication of cancer genetic test results in a diverse population. Translational behavioral medicine Ricker, C. N., Koff, R. B., Qu, C. n., Culver, J. n., Sturgeon, D. n., Kingham, K. E., Lowstuter, K. n., Chun, N. M., Rowe-Teeter, C. n., Lebensohn, A. n., Levonian, P. n., Partynski, K. n., Lara-Otero, K. n., Hong, C. n., Petrovchich, I. M., Mills, M. A., Hartman, A. R., Allen, B. n., Ladabaum, U. n., McDonnell, K. n., Ford, J. M., Gruber, S. B., Kurian, A. W., Idos, G. E. 2018; 8 (1): 85–94

  Abstract

  Research on the communication of genetic test results has focused predominately on non-Hispanic White (NHW) mutation-positive families with high-risk hereditary cancer conditions. Little is known about this process for racially and ethnically diverse individuals or for those with mutations in moderate risk genes. The communication behaviors of study participants who carry a gene mutation were analyzed 3 months after disclosure of genetic test results. Participants were queried about communication of their results, as part of a prospective study of multi-gene panel genetic testing. The responses of particpants who tested positive were analyzed by race/ethnicity and by level of cancer risk (high vs. moderate). Of the 216 mutation-positive study participants, 136 (63%) responded. Self-reported race/ethnicity was 46% NHW, 41% Hispanic, 10% Asian, and 2% Black. The majority (99.0%, n = 135) had shared their results with someone and 96% had told a family member (n = 130). Hispanic respondents were less likely to have told a healthcare provider about their results than NHW (29% vs. 68%, p < .0001). Asian respondents were less likely than NHW to encourage family members to undergo testing (OR = 0.1, p = .03); but Asian family members were more likely to undergo testing (OR = 8.0, p = .03). There were no differences in communication between those with a mutation in a high- or moderate-risk gene. Three months post genetic testing, communication of results was very high; 30% reported a family member underwent genetic testing. Further studies are needed to better understand the communication process in individuals from diverse racial/ethnic backgrounds.

  View details for PubMedID 29385580

• Measuring serum melatonin in postmenopausal women: Implications for epidemiologic studies and breast cancer studies. PloS one Chu, L. W., John, E. M., Yang, B. n., Kurian, A. W., Zia, Y. n., Yu, K. n., Ingles, S. A., Stanczyk, F. Z., Hsing, A. W. 2018; 13 (4): e0195666

  Abstract

  Circulating melatonin is a good candidate biomarker for studies of circadian rhythms and circadian disruption. However, epidemiologic studies on circulating melatonin are limited because melatonin is secreted at night, yet most epidemiologic studies collect blood during the day when melatonin levels are very low, and assays are lacking that are ultrasensitive to detect low levels of melatonin reliably.To assess the performance of a refined radioimmunoassay in measuring morning melatonin among women.We used morning serum samples from 47 postmenopausal women ages 48-80 years without a history of breast cancer who participated in the San Francisco Bay Area Breast Cancer Study, including 19 women who had duplicate measurements. The coefficient of variation (CV) and intraclass coefficient (ICC) were estimated using the random effect model.Reproducibility for the assay was satisfactory, with a CV of 11.2% and an ICC of 98.9%; correlation between the replicate samples was also high (R = 0.96). In the 47 women, serum melatonin levels ranged from 0.6 to 62.6 pg/ml, with a median of 7.0 pg/ml.Our results suggest that it is possible to reliably measure melatonin in postmenopausal women in morning serum samples in large epidemiologic studies to evaluate the role of melatonin in cancer etiology or prognosis.

  View details for PubMedID 29641614

• Differences in Breast Cancer Survival by Molecular Subtypes in the United States. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Howlader, N. n., Cronin, K. A., Kurian, A. W., Andridge, R. n. 2018

  Abstract

  While incidence rates of breast cancer molecular subtypes are well documented, effects of molecular subtypes on breast cancer-specific survival using largest population coverage to date are unknown in the U.S.Using SEER (Surveillance, Epidemiology and End Results) cancer registry data, we assessed survival after breast cancer diagnosis among women diagnosed during 2010-2013 and followed through 12/31/2014. Breast cancer molecular subtypes defined by joint hormone receptor (HR, estrogen receptor [ER] and/or progesterone receptor [PR]) and HER2 status were assessed. Multiple imputation was used to fill in missing receptor status. Four-year breast cancer-specific survival per molecular subtypes and clinical/demographic factors were calculated. A cox proportional hazards model was used to evaluate survival while controlling for clinical and demographic factors.The best survival pattern was observed among women with HR+/HER2- subtype (survival rate of 92.5% at four years), followed by HR+/HER2+ (90.3%), HR-/HER2+ (82.7%), and finally worst survival for triple-negative subtype (77.0%). Notably, failing to impute cases with missing receptor status leads to overestimation of survival because those with missing receptor status tend to have worse prognostic features. Survival differed substantially by stage at diagnosis. Among de novo stage IV disease, women with HR+/HER2+ subtype experienced better survival than those with HR+/HER2- subtype (45.5% vs 35.9%), even after controlling for other factors.Divergence of survival curves in stage IV HR+/HER2+ vs. HR+/HER2- subtype is likely attributable to major advances in HER2-targeted treatment.Contrary to conventional thought, HR+/HER2+ subtype experienced better survival than HR+/HER2- in advanced stage disease.

  View details for PubMedID 29593010

• Patient Experiences and Clinician Views on the Role of Radiation Therapy for Ductal Carcinoma In Situ. International journal of radiation oncology, biology, physics Shumway, D. A., McLeod, C. M., Morrow, M. n., Li, Y. n., Kurian, A. W., Sabolch, A. n., Hamilton, A. S., Ward, K. C., Katz, S. J., Hawley, S. T., Jagsi, R. n. 2018

  Abstract

  To evaluate patient experiences with decisions regarding radiation therapy (RT) for ductal carcinoma in situ (DCIS), and to assess clinician views on the role of RT for DCIS with favorable features in the present era.A sample of women with newly diagnosed breast cancer from the population-based Georgia and Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registries were sent surveys approximately 2 months after undergoing breast-conserving surgery (BCS), with a 70% response rate. The analytic sample was limited to 538 respondents with unilateral DCIS. We also surveyed 761 surgeons and radiation oncologists treating breast cancer in those regions, of whom, 539 responded (71%).After BCS, 23% of patients omitted RT, with twice the rate of omission in Los Angeles County relative to Georgia (31% vs 16%; P < .001). The most common reasons for omitting RT were advice from a clinician that it was not needed (62%) and concern about side effects (24%). Cost and transportation were not reported as influential considerations. After covariate adjustment, low- and intermediate-grade disease (odds ratio [OR] 5.5, 95% confidence interval [CI] 2.5-12; and OR 3.2, 95% CI 1.7-6.1, respectively) and Los Angeles County SEER site (OR 4.3, 95% CI 2.3-8.2) were significantly associated with greater RT omission. Of the responding clinicians, 62% would discuss RT omission for a patient with DCIS with favorable features. Clinicians in Los Angeles County were more likely to discuss RT omission than were those in Georgia (67% vs 56%; P = .01). Approximately one third of clinicians would obtain the Oncotype DX DCIS score.The heterogeneity in RT omission after BCS for DCIS continues to be substantial, with systematic differences in provider opinions across the 2 regions we studied. Enhanced precision of recurrence estimates, guidance from professional organizations, and better communication are needed to improve the consistency of treatment in this controversial area.

  View details for PubMedID 29439886

• Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012. JAMA Plevritis, S. K., Munoz, D. n., Kurian, A. W., Stout, N. K., Alagoz, O. n., Near, A. M., Lee, S. J., van den Broek, J. J., Huang, X. n., Schechter, C. B., Sprague, B. L., Song, J. n., de Koning, H. J., Trentham-Dietz, A. n., van Ravesteyn, N. T., Gangnon, R. n., Chandler, Y. n., Li, Y. n., Xu, C. n., Ergun, M. A., Huang, H. n., Berry, D. A., Mandelblatt, J. S. 2018; 319 (2): 154–64

  Abstract

  Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden.To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu).Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated.Screening mammography and treatment.The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment.In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2-, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER-/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER-/ERBB2-, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%).In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.

  View details for PubMedID 29318276

• Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women. JCO precision oncology Kurian, A. W., Hughes, E., Handorf, E. A., Gutin, A., Allen, B., Hartman, A. R., Hall, M. J. 2017; 1: 1-12

  Abstract

  Multiple-gene, next-generation sequencing panels are increasingly used to assess hereditary cancer risks of patients with diverse personal and family cancer histories. The magnitude of breast and ovarian cancer risk associated with many clinically tested genes, and independent of family cancer history, remains to be quantified.We queried a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene (APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53) next-generation sequencing panel. Multivariable logistic regression models accounting for family history were used to examine the association between pathogenic mutations and breast or ovarian cancer. As a confirmatory approach, a matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer.One or more pathogenic mutations were detected in 6,775 (7%) of 95,561 women. Eight genes (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios (ORs) ranging from two-fold (ATM: OR, 1.74; 95% CI, 1.46 to 2.07) to six-fold (BRCA1: OR, 5.91; 95% CI, 5.25 to 6.67). Eleven genes (ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with OR ranging from two-fold (ATM: OR, 1.69; 95% CI, 1.19 to 2.40) to 40-fold (STK11: OR, 41.9; 95% CI, 5.55 to 315). Multivariable models and matched case-control analyses yielded similar results.Among nearly 100,000 clinically tested women, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. These results may inform cancer risk counseling.

  View details for DOI 10.1200/PO.16.00066

  View details for PubMedID 35172496

• Pathogenic germline mutations in emerging cancer genes: What happens after panel testing? Hall, E., Parikh, D., Gupta, T., Caswell, J., Mills, M., Kingham, K., Koff, R., Ford, J. M., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.1528

  View details for Web of Science ID 000411895702184

• Recent time trends in chemotherapy use and oncologists' chemotherapy recommendations for early-stage, hormone receptor-positive breast cancer. Kurian, A. W., Bondarenko, I., Jagsi, R., McLeod, C., Hawley, S. T., Hamilton, A. S., Ward, K. C., Katz, S. J. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.541

  View details for Web of Science ID 000411895700059

• Factors associated with 21-gene assay receipt among women with lymph node positive breast cancer. Roberts, M., Kurian, A. W., Petkov, V. I. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.6554

  View details for Web of Science ID 000411931706049

• Treatment decisions and employment of breast cancer patients: Results of a population-based survey. Jagsi, R., Abrahamse, P., Lee, K., Wallner, L. P., Janz, N. K., Hamilton, A. S., Ward, K. C., Morrow, M., Kurian, A. W., Friese, C., Hawley, S. T., Katz, S. J. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.10052

  View details for Web of Science ID 000411932204178

• Performance of mutation risk prediction models in a racially diverse multi-gene panel testing cohort. Idos, G., Roth, K. G., Naghi, L., Ricker, C., Culver, J., Sturgeon, D., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Hartman, A., Allen, B., Evans, B., Mills, M., Hong, C., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.1523

  View details for Web of Science ID 000411895702179

• Expanded yield of multiplex panel testing in fully accrued prospective trial. Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Lowstuter, K., Hartman, A., Allen, B., Kidd, J., Mills, M., Ma, C., Hong, C., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.1525

  View details for Web of Science ID 000411895702181

• The Changing Landscape of Genetic Testing for Inherited Breast Cancer Predisposition. Current treatment options in oncology Afghahi, A., Kurian, A. W. 2017; 18 (5): 27-?

  Abstract

  The advent of multiple-gene germline panel testing has led to significant advances in hereditary breast and ovarian cancer risk assessment. These include guideline-specific cancer risk management recommendations for patients and their families, such as screening with breast magnetic resonance imaging and risk-reducing surgeries, which have the potential to reduce substantially the morbidity and mortality associated with a hereditary cancer predisposition. However, controversy remains about the clinical validity and actionability of genetic testing in a broader patient population. We discuss events leading to the wider availability of commercialized multiple-gene germline panel testing, the recent data that support using this powerful tool to improve cancer risk assessment and reduction strategies, and remaining challenges to clinical optimization of this new genetic technology.

  View details for DOI 10.1007/s11864-017-0468-y

  View details for PubMedID 28439798

• Molecular receptor profiles in male mutation carriers with breast cancer Wapnir, I., Kingham, K., Mills, M., Ford, J., Kurian, A. SPRINGER. 2017: 112–13

  View details for Web of Science ID 000455441000079

• Gaps in integrating genetic testing into management of breast cancer. Katz, S. J., Hawley, S. T., Jagsi, R., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.8_suppl.160

  View details for Web of Science ID 000443301600159

• Contralateral Prophylactic Mastectomy Decisions in a Population-Based Sample of Patients With Early-Stage Breast Cancer JAMA SURGERY Jagsi, R., Hawley, S. T., Griffith, K. A., Janz, N. K., Kurian, A., Ward, K. C., Hamilton, S., Morrow, M., Katz, S. J. 2017; 152 (3)

  Abstract

  Contralateral prophylactic mastectomy (CPM) use is increasing among women with unilateral breast cancer, but little is known about treatment decision making or physician interactions in diverse patient populations.To evaluate patient motivations, knowledge, and decisions, as well as the impact of surgeon recommendations, in a large, diverse sample of patients who underwent recent treatment for breast cancer.A survey was sent to 3631 women with newly diagnosed, unilateral stage 0, I, or II breast cancer between July 2013 and September 2014. Women were identified through the population-based Surveillance Epidemiology and End Results registries of Los Angeles County and Georgia. Data on surgical decisions, motivations for those decisions, and knowledge were included in the analysis. Logistic and multinomial logistic regression of the data were conducted to identify factors associated with (1) CPM vs all other treatments combined, (2) CPM vs unilateral mastectomy (UM), and (3) CPM vs breast-conserving surgery (BCS). Associations between CPM receipt and surgeon recommendations were also evaluated. All statistical models and summary estimates were weighted to be representative of the target population.Receipt of CPM was the primary dependent variable for analysis and was measured by a woman's self-report of her treatment.Of the 3631 women selected to receive the survey, 2578 (71.0%) responded and 2402 of these respondents who did not have bilateral disease and for whom surgery type was known constituted the final analytic sample. The mean (SD) age was 61.8 (12) years at the time of the survey. Overall, 1301 (43.9%) patients considered CPM (601 [24.8%] considered it very strongly or strongly); only 395 (38.1%) of them knew that CPM does not improve survival for all women with breast cancer. Ultimately, 1466 women (61.6%) received BCS, 508 (21.2%) underwent UM, and 428 (17.3%) received CPM. On multivariable analysis, factors associated with CPM included younger age (per 5-year increase: odds ratio [OR], 0.71; 95% CI, 0.65-0.77), white race (black vs white: OR, 0.50; 95% CI, 0.34-0.74), higher educational level (OR, 1.69; 95% CI, 1.20-2.40), family history (OR, 1.63; 95% CI, 1.22-2.17), and private insurance (Medicaid vs private insurance: OR, 0.47; 95% CI, 0.28-0.79). Among 1569 patients (65.5%) without high genetic risk or an identified mutation, 598 (39.3%) reported a surgeon recommendation against CPM, of whom only 12 (1.9%) underwent CPM, but among the 746 (46.8%) of these women who received no recommendation for or against CPM from a surgeon, 148 (19.0%) underwent CPM.Many patients consider CPM, but knowledge about the procedure is low and discussions with surgeons appear to be incomplete. Contralateral prophylactic mastectomy use is substantial among patients without clinical indications but is low when patients report that their surgeon recommended against it. More effective physician-patient communication about CPM is needed to reduce potential overtreatment.

  View details for DOI 10.1001/jamasurg.2016.4749

  View details for Web of Science ID 000398101400016

• COMMUNICATING COMPLEXITY: ANALYSIS OF THE COMMUNICATION OF CANCER GENETIC TEST RESULTS THREE MONTHS POST DISCLOSURE Ricker, C., Koff, R., Qu, C., Culver, J. O., Sturgeon, D., Lowstuter, K., Hong, C. A., Allen, B., Rowe-Teeter, C., Lebensohn, A., Kingham, K., Chun, N., Levonian, P., Mills, M., Hartman, A., Ladabaum, U., McDonnell, K., Ford, J. M., Gruber, S., Kurian, A. W., Idos, G. SPRINGER. 2017: S1540–S1541

  View details for Web of Science ID 000398947202110

• Dynamic Strategy for Personalized Medicine: An Application to Metastatic Breast Cancer. Journal of biomedical informatics Chen, X., Shachter, R., Kurian, A., Rubin, D. 2017

  Abstract

  We compare methods to develop an adaptive strategy for therapy choice in a class of breast cancer patients, as an example of approaches to personalize therapies for individual characteristics and each patient's response to therapy. Our model maintains a Markov belief about the effectiveness of the different therapies and updates it as therapies are administered and tumor images are observed, reflecting tumor response. We compare three different approximate methods to solve our analytical model against standard medical practice and show significant potential benefit of the computed dynamic strategies to limit tumor growth and to reduce the number of time periods patients are given chemotherapy, with its attendant side effects.

  View details for DOI 10.1016/j.jbi.2017.02.012

  View details for PubMedID 28232241

• The impact of doctor-patient communication on patients' perceptions of their risk of breast cancer recurrence BREAST CANCER RESEARCH AND TREATMENT Janz, N. K., Li, Y., Zikmund-Fisher, B. J., Jagsi, R., Kurian, A. W., An, L. C., McLeod, M. C., Lee, K. L., Katz, S. J., Hawley, S. T. 2017; 161 (3): 525-535

  Abstract

  Doctor-patient communication is the primary way for women diagnosed with breast cancer to learn about their risk of distant recurrence. Yet little is known about how doctors approach these discussions.A weighted random sample of newly diagnosed early-stage breast cancer patients identified through SEER registries of Los Angeles and Georgia (2013-2015) was sent surveys about ~2 months after surgery (Phase 2, N = 3930, RR 68%). We assessed patient perceptions of doctor communication of risk of recurrence (i.e., amount, approach, inquiry about worry). Clinically determined 10-year risk of distant recurrence was established for low and intermediate invasive cancer patients. Women's perceived risk of distant recurrence (0-100%) was categorized into subgroups: overestimation, reasonably accurate, and zero risk. Understanding of risk and patient factors (e.g. health literacy, numeracy, and anxiety/worry) on physician communication outcomes was evaluated in multivariable regression models (analytic sample for substudy = 1295).About 33% of women reported that doctors discussed risk of recurrence as "quite a bit" or "a lot," while 14% said "not at all." Over half of women reported that doctors used words and numbers to describe risk, while 24% used only words. Overestimators (OR .50, CI 0.31-0.81) or those who perceived zero risk (OR .46, CI 0.29-0.72) more often said that their doctor did not discuss risk. Patients with low numeracy reported less discussion. Over 60% reported that their doctor almost never inquired about worry.Effective doctor-patient communication is critical to patient understanding of risk of recurrence. Efforts to enhance physicians' ability to engage in individualized communication around risk are needed.

  View details for DOI 10.1007/s10549-016-4076-5

  View details for Web of Science ID 000393023500014

  View details for PubMedID 27943007

• The influence of 21-gene recurrence score assay on chemotherapy use in a population-based sample of breast cancer patients BREAST CANCER RESEARCH AND TREATMENT Li, Y., Kurian, A. W., Bondarenko, I., Taylor, J. M., Jagsi, R., Ward, K. C., Hamilton, A. S., Katz, S. J., Hofer, T. P. 2017; 161 (3): 587-595

  Abstract

  To quantify the influence of RS assay on changing chemotherapy plans in a general practice setting using causal inference methods.We surveyed 3880 newly diagnosed breast cancer patients in Los Angeles and Georgia in 2013-14. We used inverse propensity weighting and multiple imputations to derive complete information for each patient about treatment status with and without testing.A half of the 1545 women eligible for testing (ER+ or PR+, HER2-, and stage I-II) received RS. We estimate that 30% (95% confidence interval (CI) 10-49%) of patients would have changed their treatment selections after RS assay, with 10% (CI 0-20%) being encouraged to undergo chemotherapy and 20% (CI 10-30%) being discouraged from chemotherapy. The subgroups whose treatment selections would be changed the most by RS were patients with positive nodes (44%; CI 24-64%), larger tumor (43% for tumor size >2 cm; CI 23-62%), or younger age (41% for <50 years, CI 23-58%). The assay was associated with a net reduction in chemotherapy use by 10% (CI 4-16%). The reduction was much greater for women with positive nodes (31%; CI 21-41%), larger tumor (30% for tumor size >2 cm; CI 22-38%), or younger age (22% for <50 years; CI 9-35%).RS substantially changed chemotherapy treatment selections with the largest influence among patients with less favorable pre-test prognosis. Whether this is optimal awaits the results of clinical trials addressing the utility of RS testing in selected subgroups.

  View details for DOI 10.1007/s10549-016-4086-3

  View details for Web of Science ID 000393023500020

  View details for PubMedID 28012085

• Recurrence risk perception and quality of life following treatment of breast cancer BREAST CANCER RESEARCH AND TREATMENT Hawley, S. T., Janz, N. K., Griffith, K. A., Jagsi, R., Friese, C. R., Kurian, A. W., Hamilton, A. S., Ward, K. C., Morrow, M., Wallner, L. P., Katz, S. J. 2017; 161 (3): 557-565

  Abstract

  Little is known about different ways of assessing risk of distant recurrence following cancer treatment (e.g., numeric or descriptive). We sought to evaluate the association between overestimation of risk of distant recurrence of breast cancer and key patient-reported outcomes, including quality of life and worry.We surveyed a weighted random sample of newly diagnosed patients with early-stage breast cancer identified through SEER registries of Los Angeles County & Georgia (2013-14) ~2 months after surgery (N = 2578, RR = 71%). Actual 10-year risk of distant recurrence after treatment was based on clinical factors for women with DCIS & low-risk invasive cancer (Stg 1A, ER+, HER2-, Gr 1-2). Women reported perceptions of their risk numerically (0-100%), with values ≥10% for DCIS & ≥20% for invasive considered overestimates. Perceptions of "moderate, high or very high" risk were considered descriptive overestimates. In our analytic sample (N = 927), we assessed factors correlated with both types of overestimation and report multivariable associations between overestimation and QoL (PROMIS physical & mental health) and frequent worry.30.4% of women substantially overestimated their risk of distant recurrence numerically and 14.7% descriptively. Few factors other than family history were significantly associated with either type of overestimation. Both types of overestimation were significantly associated with frequent worry, and lower QoL.Ensuring understanding of systemic recurrence risk, particularly among patients with favorable prognosis, is important. Better risk communication by clinicians may translate to better risk comprehension among patients and to improvements in QoL.

  View details for DOI 10.1007/s10549-016-4082-7

  View details for Web of Science ID 000393023500017

  View details for PubMedID 28004220

• Treatment-associated toxicities reported by patients with early-stage invasive breast cancer. Cancer Friese, C. R., Harrison, J. M., Janz, N. K., Jagsi, R., Morrow, M., Li, Y., Hamilton, A. S., Ward, K. C., Kurian, A. W., Katz, S. J., Hofer, T. P. 2017

  Abstract

  Patient-reported toxicities help to appraise the breast cancer treatment experience. Yet extant data come from clinical trials and health care claims, which may be biased. Using patient surveys, the authors sought to quantify the frequency, severity, and burden of treatment-associated toxicities.Between 2013 and 2014, the iCanCare study surveyed a population-based sample of women residing in Los Angeles County and Georgia with early-stage, invasive breast cancer. The authors assessed the frequency and severity of toxicities; correlated toxicity severity with unscheduled health care use (clinic visits, emergency department visits/hospitalizations) and physical health; and examined patient, tumor, and treatment factors associated with reporting increased toxicity severity.The overall survey response rate was 71%. From the analyzed cohort of 1945 women, 866 (45%) reported at least 1 toxicity that was severe/very severe, 9% reported unscheduled clinic visits for toxicity management, and 5% visited an emergency department or hospital. Factors associated with reporting higher toxicity severity included receipt of chemotherapy (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 2.0-2.5), receipt of both chemotherapy and radiotherapy (OR, 1.3; 95% CI, 1.0-1.7), and Latina ethnicity (OR vs whites: 1.3; 95% CI, 1.1-1.5). A nonsignificant increase in at least 1 severe/very severe toxicity report was observed for bilateral mastectomy recipients (OR, 1.2; 95% CI, 1.0-1.4).Women with early-stage invasive breast cancer report substantial treatment-associated toxicities and related burden. Clinicians should collect toxicity data routinely and offer early intervention. Toxicity differences observed by treatment modality may inform decision making. Cancer 2017. © 2017 American Cancer Society.

  View details for DOI 10.1002/cncr.30547

  View details for PubMedID 28117882

• Tumor BRCA1 Reversion Mutation Arising During Neoadjuvant Platinum-Based Chemotherapy in Triple-Negative Breast Cancer Is Associated with Therapy Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research Afghahi, A., Timms, K. M., Vinayak, S., Jensen, K. C., Kurian, A. W., Carlson, R. W., Chang, P., Schackmann, E. A., Hartman, A., Ford, J. M., Telli, M. L. 2017

  Abstract

  In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy.PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80). All patients underwent comprehensive BRCA1/2 genotyping. For mutation carriers with moderate or extensive residual disease after neoadjuvant therapy, BRCA1/2 status was re-sequenced in the residual surgical breast tumor tissue.Nineteen patients had a deleterious germline BRCA1/2 mutation and 4 had moderate residual disease at surgery. BRCA1/2 sequencing of residual tissue was performed on three patients. These patients had BRCA1 1479delAG, 3374insGA and W1712X mutations, respectively, with loss of heterozygosity at these loci in the pre-treatment tumors. In the first case, a new BRCA1 mutation was detected in the residual disease. This resulted in a 14 amino acid deletion and restoration of the BRCA1 reading frame. A local relapse biopsy four months later revealed the identical reversion mutation, and the patient subsequently died of metastatic breast cancer.We report a BRCA1 reversion mutation in a newly diagnosed triple-negative breast cancer patient that developed over 18 weeks of platinum-based neoadjuvant therapy. This was associated with poor therapy response, early relapse and death.

  View details for DOI 10.1158/1078-0432.CCR-16-2174

  View details for PubMedID 28087643

• Unsupervised clustering of quantitative image phenotypes reveals breast cancer subtypes with distinct prognoses and molecular pathways. Clinical cancer research : an official journal of the American Association for Cancer Research Wu, J., Cui, Y., Sun, X., Cao, G., Li, B., Ikeda, D. M., Kurian, A. W., Li, R. 2017

  Abstract

  To identify novel breast cancer subtypes by extracting quantitative imaging phenotypes of the tumor and surrounding parenchyma, and to elucidate the underlying biological underpinnings and evaluate the prognostic capacity for predicting recurrence-free survival (RFS).We retrospectively analyzed dynamic contrast-enhanced magnetic resonance imaging data of patients from a single-center discovery cohort (n=60) and an independent multi-center validation cohort (n=96). Quantitative image features were extracted to characterize tumor morphology, intra-tumor heterogeneity of contrast agent wash-in/wash-out patterns, and tumor-surrounding parenchyma enhancement. Based on these image features, we used unsupervised consensus clustering to identify robust imaging subtypes, and evaluated their clinical and biological relevance. We built a gene expression-based classifier of imaging subtypes and tested their prognostic significance in five additional cohorts with publically available gene expression data but without imaging data (n=1160).Three distinct imaging subtypes, i.e., homogeneous intratumoral enhancing, minimal parenchymal enhancing, and prominent parenchymal enhancing, were identified and validated. In the discovery cohort, imaging subtypes stratified patients with significantly different 5-year RFS rates of 79.6%, 65.2%, 52.5% (logrank P=0.025), and remained as an independent predictor after adjusting for clinicopathological factors (hazard ratio=2.79, P=0.016). The prognostic value of imaging subtypes was further validated in five independent gene expression cohorts, with average 5-year RFS rates of 88.1%, 74.0%, 59.5% (logrank P from <0.0001 to 0.008). Each imaging subtype was associated with specific dysregulated molecular pathways that can be therapeutically targeted.Imaging subtypes provide complimentary value to established histopathological or molecular subtypes, and may help stratify breast cancer patients.

  View details for DOI 10.1158/1078-0432.CCR-16-2415

  View details for PubMedID 28073839

• Chemotherapy Decisions and Patient Experience With the Recurrence Score Assay for Early-Stage Breast Cancer CANCER Friese, C. R., Li, Y., Bondarenko, I., Hofer, T. P., Ward, K. C., Hamilton, A. S., Deapen, D., Kurian, A. W., Katz, S. J. 2017; 123 (1): 43-51

  Abstract

  The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making.This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%). Women reported chemotherapy recommendations, the receipt of chemotherapy, testing experiences, and decision satisfaction. Registries linked the tumor data, RS, and surveys. Regression models examined factors associated with chemotherapy recommendations and receipt by the RS and subgroups.There were 1527 patients with stage I/II, estrogen receptor/progesterone receptor-positive, human epidermal growth factor 2-negative disease: 778 received an RS (62.6% of patients with node-negative, favorable disease, 24.3% of patients with node-negative, unfavorable disease, and 13.0% of patients with node-positive disease; P < .001). Overall, 47.2% of the patients received a recommendation against chemotherapy, and 40.5% received a recommendation for it. RS results correlated with recommendations: nearly all patients with high scores (31-100) received a chemotherapy recommendation (86.9%-96.5% across clinical subgroups), whereas the majority of the patients with low-risk results (0-18) received a recommendation against it (65.9%-78.2% across subgroups). Most patients with high RSs received chemotherapy (87.0%, 91.1%, and 100% across subgroups), whereas few patients with low scores received it (2.9%, 9.5%, and 26.6% across subgroups). There were no substantial racial/ethnic differences in testing or treatment. Women were largely satisfied with the RS and chemotherapy decisions.Oncologists use the RS to personalize treatment, even for those with node-positive disease. High satisfaction and an absence of disparities in testing and treatment suggest that precision-medicine advances have improved systemic breast cancer treatment. Cancer 2016. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30324

  View details for Web of Science ID 000394719100007

• Gaps in integrating genetic testing into management of breast cancer. American Society of Clinical Oncology Annual Meeting Katz, S. J., Hawley, S., Jagsi, R., Kurian, A. W. 2017
• Value of cancer care for metastatic breast cancer patients and providers San Antonio Breast Cancer Symposium May, S., Chung, A., Vania, D., Hou, N., MacEwan, J., Batt, K., Kurian, A. W., et al 2017
• Breast cancer specific survival in young women <40 years with node-negative luminal breast cancer treated based on tumor gene expression European Society of Medical Oncology Annual Meeting Shak, S., Roberts, M., Miller, D., Kurian, A. W., Petkov, V., Penberthy, L. 2017
• Recent time trends in chemotherapy use and oncologists' chemotherapy recommendations for early-stage, hormone receptor-positive breast cancer. American Society of Clinical Oncology Annual Meeting Kurian, A. W., Bondarenko, I., Jagsi, R., et al 2017
• Expanded yield of multiplex panel testing in fully accrued prospective trial. American Society of Clinical Oncology Annual Meeting Idos, G., Kurian, A. W., Ricker, C., et al 2017
• Genetic counseling, germline genetic testing, and impact of results in patients with newly diagnosed breast cancer San Antonio Breast Cancer Symposium Katz, S. J., Morrow, M., Jagsi, R., Kurian, A. W. 2017
• What are the treatment patterns and overall survival in patients with metastatic triple-negative breast cancer in US clinical practice? European Society of Medical Oncology Annual Meeting Bajaj, P., Latremouille-Viau, D., Guerin, A., Reyes, C., Stein, A., Kurian, A. W., Cortazar, P. 2017
• Multiple-gene panel testing for hereditary cancer risk reveals a racial/ethnic disparity in genetic information San Antonio Breast Cancer Symposium Caswell-Jin, J., Hall, E., Mills, M., Kingham, K., Koff, R., Chun, N., Levonian, P., Lebensohn, A., Ford, J., Kurian, A. W. 2017
• Treatment decisions and employment of breast cancer patients: Results of a population-based survey. Cancer Jagsi, R. n., Abrahamse, P. H., Lee, K. L., Wallner, L. P., Janz, N. K., Hamilton, A. S., Ward, K. C., Morrow, M. n., Kurian, A. W., Friese, C. R., Hawley, S. T., Katz, S. J. 2017

  Abstract

  Many patients with breast cancer work for pay at the time of their diagnosis, and the treatment plan may threaten their livelihood. Understanding work experiences in a contemporary population-based sample is necessary to inform initiatives to reduce the burden of cancer care.Women who were 20 to 79 years old and had been diagnosed with stage 0 to II breast cancer, as reported to the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014-2015, were surveyed. Of the 3672 eligible women, 2502 responded (68%); 1006 who reported working before their diagnosis were analyzed. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for ≤1 month.In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). One-third (33%) received chemotherapy. Most (84%) worked full-time before their diagnosis; however, only 50% had paid sick leave, 39% had disability benefits, and 38% had flexible work schedules. Surgical treatment was strongly correlated with missing >1 month of work (odds ratio [OR] for bilateral mastectomy with reconstruction vs lumpectomy, 7.8) and with stopping work altogether (OR for bilateral mastectomy with reconstruction vs lumpectomy, 3.1). Chemotherapy receipt (OR for missing >1 month, 1.3; OR for stopping work altogether, 3.9) and race (OR for missing >1 month for blacks vs whites, 2.0; OR for stopping work altogether for blacks vs whites, 1.7) also correlated. Those with paid sick leave were less likely to stop working (OR, 0.5), as were those with flexible schedules (OR, 0.3).Working patients who received more aggressive treatments were more likely to experience substantial employment disruptions. Cancer 2017. © 2017 American Cancer Society.

  View details for PubMedID 28990155

• Regional Variability in Percentage of Breast Cancers Reported as Positive for HER2 in California: Implications of Patient Demographics on Laboratory Benchmarks. American journal of clinical pathology Lin, C. Y., Carneal, E. E., Lichtensztajn, D. Y., Gomez, S. L., Clarke, C. A., Jensen, K. C., Kurian, A. W., Allison, K. H. 2017; 148 (3): 199–207

  Abstract

  The expected regional variability in percent human epidermal growth factor receptor 2 (HER2)-positive breast cancers is not currently clear.Data from the 2006 to 2011 California Cancer Registry were examined by county and health service area. The influence of demographic and pathologic features was used in a multivariable logistic regression model to compare expected with observed HER2-positive percentages by region.There was significant geographic variation by California counties (11.6%-26%). The reported HER2-positive percentage was higher when the population had higher stage, tumor size, grade, percent estrogen receptor negative, younger age, or lower socioeconomic status. Ethnic distribution of the population also influenced HER2-positive percentages. Using a multivariable logistic regression model, most regions had expected values based on their population characteristics; however, "outlier" regions were identified.These results deepen our understanding of population characteristics' influence on the distribution of HER2-positive breast cancers. Taking these factors into account can be useful when setting laboratory benchmarks and assessing test quality.

  View details for PubMedID 28821197

• What Factors Influence Women's Perceptions of their Systemic Recurrence Risk after Breast Cancer Treatment? Medical decision making : an international journal of the Society for Medical Decision Making Lee, K. L., Janz, N. K., Zikmund-Fisher, B. J., Jagsi, R. n., Wallner, L. P., Kurian, A. W., Katz, S. J., Abrahamse, P. n., Hawley, S. T. 2017: 272989X17724441

  Abstract

  Breast cancer patients' misunderstanding of their systemic cancer recurrence risk has consequences on decision-making and quality of life. Little is known about how women derive their risk estimates.Using Los Angeles and Georgia's SEER registries (2014-2015), a random sample of early-stage breast cancer patients was sent surveys about 2 to 3 months after surgery ( N = 3930; RR, 68%). We conducted an inductive thematic analysis of open-ended responses about why women chose their risk estimates in a uniquely large sub-sample ( N = 1,754). Clinician estimates of systemic recurrence risk were provided for patient sub-groups with DCIS and with low-, intermediate-, and high-risk invasive disease. Women's perceived risk of systemic recurrence (0% to 100%) was categorized as overestimation, reasonably accurate estimation, or underestimation (0% for invasive disease) and was compared across identified factors and by clinical presentation.Women identified 9 main factors related to their clinical experience (e.g., diagnosis and testing; treatment) and non-clinical beliefs (e.g., uncertainty; spirituality). Women who mentioned at least one clinical experience factor were significantly less likely to overestimate their risk (12% v. 43%, P < 0.001). Most women who were influenced by "communication with a clinician" had reasonably accurate recurrence estimates (68%). "Uncertainty" and "family and personal history" were associated with overestimation, particularly for women with DCIS (75%; 84%). "Spirituality, religion, and faith" was associated with an underestimation of risk (63% v. 20%, P < 0.001).The quantification of our qualitative results is subject to any biases that may have occurred during the coding process despite rigorous methodology.Patient-clinician communication is important for breast cancer patients' understanding of their numeric risk of systemic recurrence. Clinician discussions about recurrence risk should address uncertainty and relevance of family and personal history.

  View details for PubMedID 28814131

• Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk. Genetics in medicine : official journal of the American College of Medical Genetics Caswell-Jin, J. L., Gupta, T. n., Hall, E. n., Petrovchich, I. M., Mills, M. A., Kingham, K. E., Koff, R. n., Chun, N. M., Levonian, P. n., Lebensohn, A. P., Ford, J. M., Kurian, A. W. 2017

  Abstract

  PurposeWe examined racial/ethnic differences in the usage and results of germ-line multiple-gene sequencing (MGS) panels to evaluate hereditary cancer risk.MethodsWe collected genetic testing results and clinical information from 1,483 patients who underwent MGS at Stanford University between 1 January 2013 and 31 December 2015.ResultsAsians and Hispanics presented for MGS at younger ages than whites (48 and 47 vs. 55; P = 5E-16 and 5E-14). Across all panels, the rate of pathogenic variants (15%) did not differ significantly between racial groups. Rates by gene did differ: in particular, a higher percentage of whites than nonwhites carried pathogenic CHEK2 variants (3.8% vs. 1.0%; P = 0.002). The rate of a variant of uncertain significance (VUS) result was higher in nonwhites than whites (36% vs. 27%; P = 2E-4). The probability of a VUS increased with increasing number of genes tested; this effect was more pronounced for nonwhites than for whites (1.1% absolute difference in VUS rates testing BRCA1/2 vs. 8% testing 13 genes vs. 14% testing 28 genes), worsening the disparity.ConclusionIn this diverse cohort undergoing MGS testing, pathogenic variant rates were similar between racial/ethnic groups. By contrast, VUS results were more frequent among nonwhites, with potential significance for the impact of MGS testing by race/ethnicity.GENETICS in MEDICINE advance online publication, 27 July 2017; doi:10.1038/gim.2017.96.

  View details for PubMedID 28749474

• Oncologists' influence on receipt of adjuvant chemotherapy: does it matter whom you see for treatment of curable breast cancer? Breast cancer research and treatment Katz, S. J., Hawley, S. T., Bondarenko, I. n., Jagsi, R. n., Ward, K. C., Hofer, T. P., Kurian, A. W. 2017

  Abstract

  We know little about whether it matters which oncologist a breast cancer patient sees with regard to receipt of chemotherapy. We examined oncologists' influence on use of recurrence score (RS) testing and chemotherapy in the community.We identified 7810 women with stages 0-II breast cancer treated in 2013-15 through the SEER registries of Georgia and Los Angeles County. Surveys were sent 2 months post-surgery, (70% response rate, n = 5080). Patients identified their oncologists (n = 504) of whom 304 responded to surveys (60%). We conducted multi-level analyses on patients with ER-positive HER2-negative invasive disease (N = 2973) to examine oncologists' influence on variation in RS testing and chemotherapy receipt, using patient and oncologist survey responses merged to SEER data.Half of patients (52.8%) received RS testing and 27.7% chemotherapy. One-third (35.9%) of oncologists treated >50 new breast cancer patients annually; mean years in practice was 15.8. Oncologists explained 17% of the variation in RS testing but little of the variation in chemotherapy receipt (3%) controlling for clinical factors. Patients seeing an oncologist who was one standard deviation above the mean use of RS testing had over two-times higher odds of receiving RS (2.47, 95% CI 1.47-4.15), but a parallel estimate of the association of oncologist with the odds of receiving chemotherapy was much smaller (1.39, CI 1.03-1.88).Clinical algorithms have markedly reduced variation in chemotherapy use across oncologists. Oncologists' large influence on variation in RS use suggests that they variably seek tumor profiling to inform treatment decisions.

  View details for PubMedID 28689364

• Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer. Radiology Wu, J. n., Li, B. n., Sun, X. n., Cao, G. n., Rubin, D. L., Napel, S. n., Ikeda, D. M., Kurian, A. W., Li, R. n. 2017: 162823

  Abstract

  Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 patients. By using data from The Cancer Genome Atlas (TCGA), a radiogenomic map for the tumor-adjacent parenchymal tissue was created and molecular pathways associated with prognostic parenchymal imaging features were identified. Furthermore, a multigene signature of the parenchymal imaging feature was built in a training cohort (n = 126), and its prognostic relevance was evaluated in two independent cohorts (n = 879 and 159). Results One image feature measuring heterogeneity (ie, information measure of correlation) was significantly associated with prognosis (false-discovery rate < 0.1), and at a cutoff of 0.57 stratified patients into two groups with different recurrence-free survival rates (log-rank P = .024). The tumor necrosis factor signaling pathway was identified as the top enriched pathway (hypergeometric P < .0001) among genes associated with the image feature. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R(2) = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. The prognostic value was confirmed in another independent cohort (Gene Expression Omnibus GSE 1456), with log-rank P = .00058 for recurrence-free survival and log-rank P = .0026 for overall survival. Conclusion Heterogeneous enhancement patterns of tumor-adjacent parenchyma at MR imaging are associated with the tumor necrosis signaling pathway and poor survival in breast cancer. (©) RSNA, 2017 Online supplemental material is available for this article.

  View details for PubMedID 28708462

• Trends in Reoperation After Initial Lumpectomy for Breast Cancer: Addressing Overtreatment in Surgical Management. JAMA oncology Morrow, M. n., Abrahamse, P. n., Hofer, T. P., Ward, K. C., Hamilton, A. S., Kurian, A. W., Katz, S. J., Jagsi, R. n. 2017

  Abstract

  Surgery after initial lumpectomy to obtain more widely clear margins is common and may lead to mastectomy.To describe surgeons' approach to surgical margins for invasive breast cancer, and changes in postlumpectomy surgery rates, and final surgical treatment following a 2014 consensus statement endorsing a margin of "no ink on tumor."This was a population-based cohort survey study of 7303 eligible women ages 20 to 79 years with stage I and II breast cancer diagnosed in 2013 to 2015 and identified from the Georgia and Los Angeles County, California, Surveillance, Epidemiology, and End Results registries. A total of 5080 (70%) returned a survey. Those with bilateral disease, missing stage or treatment data, and with ductal carcinoma in situ were excluded, leaving 3729 patients in the analytic sample; 98% of these identified their attending surgeon. Between April 2015 and May 2016, 488 surgeons were surveyed regarding lumpectomy margins; 342 (70%) responded completely. Pathology reports of all patients having a second surgery and a 30% sample of those with 1 surgery were reviewed. Time trends were analyzed with multinomial regression models.Rates of final surgical procedure (lumpectomy, unilateral mastectomy, bilateral mastectomy) and rates of additional surgery after initial lumpectomy over time, and surgeon attitudes toward an adequate lumpectomy margin.The 67% rate of initial lumpectomy in the 3729 patient analytic sample was unchanged during the study. The rate of final lumpectomy increased by 13% from 2013 to 2015, accompanied by a decrease in unilateral and bilateral mastectomy (P = .002). Surgery after initial lumpectomy declined by 16% (P < .001). Pathology review documented no significant association between date of treatment and positive margins. Of 342 responding surgeons, 69% endorsed a margin of no ink on tumor to avoid reexcision in estrogen receptor-positive progesterone receptor-positive cancer and 63% for estrogen receptor-negative progesterone- receptor-negative cancer. Surgeons treating more than 50 breast cancers annually were significantly more likely to report this margin as adequate (85%; n = 105) compared with those treating 20 cases or fewer (55%; n = 131) (P < .001).Additional surgery after initial lumpectomy decreased markedly from 2013 to 2015 concomitant with dissemination of clinical guidelines endorsing a minimal negative margin. These findings suggest that surgeon-led initiatives to address potential overtreatment can reduce the burden of surgical management in patients with cancer.

  View details for PubMedID 28586788

• NCCN Guidelines (R) Insights Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Daly, M. B., Pilarski, R., Berry, M., Buys, S. S., Farmer, M., Friedman, S., Garber, J. E., Kauff, N. D., Khan, S., Klein, C., Kohlmann, W., Kurian, A., Litton, J. K., Madlensky, L., Merajver, S. D., Offit, K., Pal, T., Reiser, G., Shannon, K. M., Swisher, E., Vinayak, S., Voian, N. C., Weitzel, J. N., Wick, M. J., Wiesner, G. L., Dwyer, M., Darlow, S. 2017; 15 (1): 9-19

  Abstract

  The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.

  View details for Web of Science ID 000392045900003

• Reply to Comment on 'Statin use and all-cancer survival: prospective results from the Women's Health Initiative'. British journal of cancer Wang, A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Chlebowski, R. T., Simon, M., Desai, P., Wassertheil-Smoller, S., Liu, S., Kritchevsky, S., Wakelee, H. A., Stefanick, M. L. 2017; 116 (3)

  View details for DOI 10.1038/bjc.2016.396

  View details for PubMedID 27923034

• Payer Coverage for Hereditary Cancer Panels: Barriers, Opportunities, and Implications for the Precision Medicine Initiative. Journal of the National Comprehensive Cancer Network : JNCCN Trosman, J. R., Weldon, C. B., Douglas, M. P., Kurian, A. W., Kelley, R. K., Deverka, P. A., Phillips, K. A. 2017; 15 (2): 219–28

  Abstract

  Background: Hereditary cancer panels (HCPs), testing for multiple genes and syndromes, are rapidly transforming cancer risk assessment but are controversial and lack formal insurance coverage. We aimed to identify payers' perspectives on barriers to HCP coverage and opportunities to address them. Comprehensive cancer risk assessment is highly relevant to the Precision Medicine Initiative (PMI), and payers' considerations could inform PMI's efforts. We describe our findings and discuss them in the context of PMI priorities. Methods: We conducted semi-structured interviews with 11 major US payers, covering >160 million lives. We used the framework approach of qualitative research to design, conduct, and analyze interviews, and used simple frequencies to further describe findings. Results: Barriers to HCP coverage included poor fit with coverage frameworks (100%); insufficient evidence (100%); departure from pedigree/family history-based testing toward genetic screening (91%); lacking rigor in the HCP hybrid research/clinical setting (82%); and patient transparency and involvement concerns (82%). Addressing barriers requires refining HCP-indicated populations (82%); developing evidence of actionability (82%) and pathogenicity/penetrance (64%); creating infrastructure and standards for informing and recontacting patients (45%); separating research from clinical use in the hybrid clinical-research setting (44%); and adjusting coverage frameworks (18%). Conclusions: Leveraging opportunities suggested by payers to address HCP coverage barriers is essential to ensure patients' access to evolving HCPs. Our findings inform 3 areas of the PMI: addressing insurance coverage to secure access to future PMI discoveries; incorporating payers' evidentiary requirements into PMI's research agenda; and leveraging payers' recommendations and experience to keep patients informed and involved.

  View details for PubMedID 28188191

• Synergistic drug combinations from electronic health records and gene expression. Journal of the American Medical Informatics Association Low, Y. S., Daugherty, A. C., Schroeder, E. A., Chen, W., Seto, T., Weber, S., Lim, M., Hastie, T., Mathur, M., Desai, M., Farrington, C., Radin, A. A., Sirota, M., Kenkare, P., Thompson, C. A., Yu, P. P., Gomez, S. L., Sledge, G. W., Kurian, A. W., Shah, N. H. 2016

  Abstract

  Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.This is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing.

  View details for DOI 10.1093/jamia/ocw161

  View details for PubMedID 27940607

• Protective Effects of Statins in Cancer: Should They Be Prescribed for High-Risk Patients? Current atherosclerosis reports Wang, A., Wakelee, H. A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Stefanick, M. L. 2016; 18 (12): 72-?

  Abstract

  Statins are one of the most widely prescribed drug classes in the USA. This review aims to summarize recent research on the relationship between statin use and cancer outcomes, in the context of clinical guidelines for statin use in patients with cancer or who are at high risk for cancer.A growing body of research has investigated the relationship between statins and cancer with mixed results. Cancer incidence has been more extensively studied than cancer survival, though results are inconsistent as some large meta-analyses have not found an association, while other studies have reported improved cancer outcomes with the use of statins. Additionally, two large studies reported increased all-cancer survival with statin use. Studies on specific cancer types in relation to cancer use have also been mixed, though the most promising results appear to be found in gastrointestinal cancers. Few studies have reported an increased risk of cancer incidence or decreased survival with statin use, though this type of association has been more commonly reported for cutaneous cancers. The overall literature on statins in relation to cancer incidence and survival is mixed, and additional research is warranted before any changes in clinical guidelines can be recommended. Future research areas include randomized controlled trials, studies on specific cancer types in relation to statin use, studies on populations without clinical indication for statins, elucidation of underlying biological mechanisms, and investigation of different statin types. However, studies seem to suggest that statins may be protective and are not likely to be harmful in the setting of cancer, suggesting that cancer patients who already take statins should not have this medication discontinued.

  View details for PubMedID 27796821

• Equivalent survival after nipple-sparing compared to non-nipple-sparing mastectomy: data from California, 1988-2013. Breast cancer research and treatment Kurian, A. W., Canchola, A. J., Gomez, S. L., Clarke, C. A. 2016; 160 (2): 333-338

  Abstract

  Nipple-sparing mastectomy, which may improve cosmesis, body image, and sexual function in comparison to non-nipple-sparing mastectomy, is increasingly used to treat early-stage breast cancer; however, long-term survival data are lacking. We evaluated survival after nipple-sparing mastectomy versus non-nipple-sparing mastectomy in a population-based cancer registry.We conducted an observational study using the California Cancer Registry, considering all stage 0-III breast cancers diagnosed in California from 1988 to 2013. We compared breast cancer-specific and overall survival time after nipple-sparing versus non-nipple-sparing mastectomy, using multivariable analysis.Among 157,592 stage 0-III female breast cancer patients treated with unilateral mastectomy from 1988-2013, 993 (0.6 %) were reported as having nipple-sparing and 156,599 (99.4 %) non-nipple-sparing mastectomies; median follow-up was 7.9 years. The proportion of mastectomies that were nipple-sparing increased over time (1988, 0.2 %; 2013, 5.1 %) and with neighborhood socioeconomic status, and decreased with age and stage. On multivariable analysis, nipple-sparing mastectomy was associated with a lower risk of breast cancer-specific mortality compared to non-nipple-sparing mastectomy [hazard ratio (HR) 0.71, 95 % confidence interval (CI) 0.51-0.98]. However, when restricting to diagnoses 1996 or later and adjusting for a larger set of covariates, risk was attenuated (HR 0.86, 95 % CI 0.52-1.42).Among California breast cancer patients diagnosed from 1988-2013, nipple-sparing mastectomy was not associated with worse survival than non-nipple-sparing mastectomy. These results may inform the decisions of patients and doctors deliberating between these surgical approaches for breast cancer treatment.

  View details for PubMedID 27665587

• Rising Bilateral Mastectomy Rates Among Neoadjuvant Chemotherapy Recipients in California From 1998 to 2012. Annals of surgery Wapnir, I. L., Kurian, A. W., Lichtensztajn, D. Y., Clarke, C. A., Gomez, S. L. 2016: -?

  Abstract

  To study the impact of rising bilateral mastectomy rates among neoadjuvant chemotherapy (NAC) recipients in California.NAC for operable breast cancer (BC) can downstage disease and facilitate breast conservation. We assessed trends in NAC use and surgical procedures in California from January 1, 1998 to December 31, 2012 using statewide population-based cancer registry data.A total of 236,797 females diagnosed with stage I-III BC were studied. Information regarding NAC, adjuvant chemotherapy (aCT), breast conserving surgery (BCS), bilateral mastectomy (BLM), and unilateral mastectomy (ULM) was abstracted from the medical records. Multivariable polytomous logistic regression was used to estimate odds ratios (OR) of receiving NAC and of type of surgery after NAC.Approximately, 40.1% (94,980) of patients received chemotherapy: 87% (82,588) aCT and 13.0% (12,392) NAC. NAC use more than doubled over time and increased with stage (Stage I, 0.7%; Stage III, 29.9%). Multivariable predictors of NAC treatment were stage (III), younger age (<40 yrs), Black or Hispanic race/ethnicity versus non-Hispanic White (OR 1.10, 95% confidence interval (CI) 1.05-1.16), and care at a National Cancer Institute (NCI)-designated center (OR 1.70, CI 1.58-1.82). Most NAC recipients (68.4%) had mastectomies, and 14.3% of them underwent BLM. In contrast, 47.9% aCT patients had mastectomies with 7.3% BLM. The only independent predictor of BCS after NAC was care at a NCI-designated center (OR 1.28, CI 1.10-1.49), and of BLM, age <40 years versus 50 to 64 years (OR 2.59, CI 2.21-3.03), or residence in the highest socioeconomic neighborhood quintile versus lowest (OR 2.10, CI 1.67-2.64).NAC use remains low. Predictors of surgery type after NAC were sociodemographic rather than clinical, raising concern for disparities in care access.

  View details for PubMedID 27611617

• Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population. Cancer causes & control Tao, L., Chu, L., Wang, L. I., Moy, L., Brammer, M., Song, C., Green, M., Kurian, A. W., Gomez, S. L., Clarke, C. A. 2016; 27 (9): 1127-1138

  Abstract

  To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression.We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality.Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer.De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

  View details for DOI 10.1007/s10552-016-0791-9

  View details for PubMedID 27496200

• The Effect of Patient and Contextual Characteristics on Racial/Ethnic Disparity in Breast Cancer Mortality CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Sposto, R., Keegan, T. H., Vigen, C., Kwan, M. L., Bernstein, L., John, E. M., Cheng, I., Yang, J., Koo, J., Kurian, A. W., Caan, B. J., Lu, Y., Monroe, K. R., Shariff-Marco, S., Gomez, S. L., Wu, A. H. 2016; 25 (7): 1064-1072

  Abstract

  Racial/ethnic disparity in breast cancer-specific mortality in the U.S. is well documented. We examined whether accounting for racial/ethnic differences in the prevalence of clinical, patient, and lifestyle and contextual factors that are associated with breast cancer-specific mortality can explain this disparity.The California Breast Cancer Survivorship Consortium combined interview data from six California-based breast cancer studies with cancer registry data to create a large racially diverse cohort of women with primary invasive breast cancer. We examined the contribution of variables in a previously reported Cox regression baseline model plus additional contextual, physical activity, body size, and comorbidity variables to the racial/ethnic disparity in breast cancer-specific mortality.The cohort comprised 12,098 women. Fifty-four percent were non-Latina Whites, 17% African Americans, 17% Latinas, and 12% Asian Americans. In a model adjusting only for age and study, breast cancer-specific hazard ratios relative to Whites were 1.69 (95% CI 1.46 - 1.96), 1.00 (0.84 - 1.19), and 0.52 (0.33 - 0.85) for African Americans, Latinas, and Asian Americans respectively. Adjusting for baseline-model variables decreased disparity primarily by reducing the hazard ratio for African Americans to 1.13 (0.96 - 1.33). The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. Other variables had negligible impact on disparity.While contextual, physical activity, body size, and comorbidity variables may influence breast cancer-specific mortality, they do not explain racial/ethnic mortality disparity.Other factors besides those investigated here may explain the existing racial/ethnic disparity in mortality.

  View details for DOI 10.1158/1055-9965.EPI-15-1326

  View details for PubMedID 27197297

• Statin use and all-cancer survival: prospective results from the Women's Health Initiative BRITISH JOURNAL OF CANCER Wang, A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Chlebowski, R. T., Simon, M., Desai, P., Wassertheil-Smoller, S., Liu, S., Kritchevsky, S., Wakelee, H. A., Stefanick, M. L. 2016; 115 (1): 129-135

  Abstract

  This study aims to investigate the association between statin use and all-cancer survival in a prospective cohort of postmenopausal women, using data from the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT).The WHI study enrolled women aged 50-79 years from 1993 to 1998 at 40 US clinical centres. Among 146 326 participants with median 14.6 follow-up years, 23 067 incident cancers and 3152 cancer deaths were observed. Multivariable-adjusted Cox proportional hazards models were used to investigate the relationship between statin use and cancer survival.Compared with never-users, current statin use was associated with significantly lower risk of cancer death (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.71-0.86, P<0.001) and all-cause mortality (HR, 0.80; 95% CI, 0.74-0.88). Use of other lipid-lowering medications was also associated with increased cancer survival (P-interaction (int)=0.57). The lower risk of cancer death was not dependent on statin potency (P-int=0.22), lipophilicity/hydrophilicity (P-int=0.43), type (P-int=0.34) or duration (P-int=0.33). However, past statin users were not at lower risk of cancer death compared with never-users (HR, 1.06; 95% CI, 0.85-1.33); in addition, statin use was not associated with a reduction of overall cancer incidence despite its effect on survival (HR, 0.96; 95% CI, 0.92-1.001).In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications was associated with decreased cancer death, regardless of the type, duration, or potency of statin medications used.British Journal of Cancer advance online publication, 9 June 2016; doi:10.1038/bjc.2016.149 www.bjcancer.com.

  View details for DOI 10.1038/bjc.2016.149

  View details for PubMedID 27280630

• Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information. American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting Kurian, A. W., Antoniou, A. C., Domchek, S. M. 2016; 35: 44-56

  Abstract

  Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival.

  View details for DOI 10.14694/EDBK_158817

  View details for PubMedID 27249685

• Use of Gene Expression Profiling and Chemotherapy in Early-Stage Breast Cancer: A Study of Linked Electronic Medical Records, Cancer Registry Data, and Genomic Data Across Two Health Care Systems. Journal of oncology practice / American Society of Clinical Oncology Afghahi, A., Mathur, M., Thompson, C. A., Mitani, A., Rigdon, J., Desai, M., Yu, P. P., de Bruin, M. A., Seto, T., Olson, C., Kenkare, P., Gomez, S. L., Das, A. K., Luft, H. S., Sledge, G. W., Sing, A. P., Kurian, A. W. 2016; 12 (6): e697-709

  Abstract

  The 21-gene recurrence score (RS) identifies patients with breast cancer who derive little benefit from chemotherapy; it may reduce unwarranted variability in the use of chemotherapy. We tested whether the use of RS seems to guide chemotherapy receipt across different cancer care settings.We developed a retrospective cohort of patients with breast cancer by using electronic medical record data from Stanford University (hereafter University) and Palo Alto Medical Foundation (hereafter Community) linked with demographic and staging data from the California Cancer Registry and RS results from the testing laboratory (Genomic Health Inc., Redwood City, CA). Multivariable analysis was performed to identify predictors of RS and chemotherapy use.In all, 10,125 patients with breast cancer were diagnosed in the University or Community systems from 2005 to 2011; 2,418 (23.9%) met RS guidelines criteria, of whom 15.6% received RS. RS was less often used for patients with involved lymph nodes, higher tumor grade, and age < 40 or ≥ 65 years. Among RS recipients, chemotherapy receipt was associated with a higher score (intermediate v low: odds ratio, 3.66; 95% CI, 1.94 to 6.91). A total of 293 patients (10.6%) received care in both health care systems (hereafter dual use); although receipt of RS was associated with dual use (v University: odds ratio, 1.73; 95% CI, 1.18 to 2.55), there was no difference in use of chemotherapy after RS by health care setting.Although there was greater use of RS for patients who sought care in more than one health care setting, use of chemotherapy followed RS guidance in University and Community health care systems. These results suggest that precision medicine may help optimize cancer treatment across health care settings.

  View details for DOI 10.1200/JOP.2015.009803

  View details for PubMedID 27221993

  View details for PubMedCentralID PMC4957259

• Yield of multiplex panel testing compared to expert opinion and validated prediction models. Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Lowstuter, K., Hartman, A., Allen, B., Kingham, K., Koff, R., Rowe-Teeter, C., Chun, N. M., Mills, M., Petrovchich, I., Hong, C., Kidd, J., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.1509

  View details for Web of Science ID 000404665402059

• Magnitude of invasive breast cancer (BC) risk associated with mutations detected by multiple-gene germline sequencing in 95,561 women. Hall, M. J., Hughes, E., Handorf, E., Gutin, A., Allen, B., Hartman, A., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.1512

  View details for Web of Science ID 000404665402062

• Association of ovarian cancer (OC) risk with mutations detected by multiple-gene germline sequencing in 95,561 women. Kurian, A. W., Hughes, E., Handorf, E., Gutin, A., Allen, B., Hartman, A., Hall, M. J. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.5510

  View details for Web of Science ID 000404711501186

• Clinical use of the 21-gene assay and patient experiences in early-stage breast cancer Katz, S. J., Friese, C., Deapen, Y., Hamilton, A. S., Ward, K. C., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6501

  View details for Web of Science ID 000404711503035

• Compliance with guidelines and factors associated with ordering the 21-gene breast cancer assay Petkov, V. I., Howlader, N., Cronin, K., Kurian, A. W., Penberthy, L. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6552

  View details for Web of Science ID 000404711503080

• Dissemination of 21-gene assay testing among female breast cancer patients in the US Cronin, K., Petkov, V. I., Howlader, N., Howe, W., Schussler, N. C., Kurian, A. W., Penberthy, L. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6553

  View details for Web of Science ID 000404711503081

• Relationship between rising bilateral mastectomy rates and increased use of neoadjuvant chemotherapy (NAC) in California, 1998-2012. Wapnir, I., Kurian, A. W., Lichtensztajn, D., Clarke, C. A., Gomez, S. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.1052

  View details for Web of Science ID 000404665401172

• Higher peripheral lymphocyte count to predict survival in triple-negative breast cancer (TNBC). Afghahi, A., Rigdon, J., Purington, N., Desal, M., Pierson, E., Mathur, M., Thompson, C. A., Curtis, C., West, R. B., Horst, K. C., Gomez, S., Ford, J. M., Sledge, G. W., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.1010

  View details for Web of Science ID 000404665401132

• Safety of multiplex gene testing for inherited cancer risk: Interim analysis of a clinical trial. Kurian, A. W., Idos, G., Culver, J., Ricker, C., Koff, R., Sturgeon, D., Lowstuter, K., Hartman, A., Allen, B., Kidd, J., Rowe-Teeter, C., Kingham, K., Chun, N. M., Petrovchich, I., Mills, M., Hong, C., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.1503

  View details for Web of Science ID 000404665402054

• Addressing Inherited Predisposition for Breast Cancer in Transplant Recipients JOURNAL OF SURGICAL ONCOLOGY Yang, R. L., Kurian, A. W., Winton, L. M., Weill, D., Patel, K., Kingham, K., Wapnir, I. L. 2016; 113 (6): 605-608

  Abstract

  Consideration of prophylactic mastectomy surgery following transplantation requires complex medical decision-making, and bias against elective surgery exists because of concern for post-operative complications. Prevention of cancer in transplant recipients is of utmost importance, given the risks of treating malignancy in an immunosuppressed patient. We present a patient case and review of the literature to support a thorough pre-transplantation evaluation of family history and consideration of prophylactic interventions to safeguard the quality of life of transplant recipients. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24193

  View details for PubMedID 26861253

• Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC). Cancer causes & control Vigen, C., Kwan, M. L., John, E. M., Gomez, S. L., Keegan, T. H., Lu, Y., Shariff-Marco, S., Monroe, K. R., Kurian, A. W., Cheng, I., Caan, B. J., Lee, V. S., Roh, J. M., Bernstein, L., Sposto, R., Wu, A. H. 2016; 27 (3): 391-401

  Abstract

  To compare information from self-report and electronic medical records for four common comorbidities (diabetes, hypertension, myocardial infarction, and other heart diseases).We pooled data from two multiethnic studies (one case-control and one survivor cohort) enrolling 1,936 women diagnosed with breast cancer, who were members of Kaiser Permanente Northern California.Concordance varied by comorbidity; kappa values ranged from 0.50 for other heart diseases to 0.87 for diabetes. Sensitivities for comorbidities from self-report versus medical record were similar for racial/ethnic minorities and non-Hispanic Whites, and did not vary by age, neighborhood socioeconomic status, or education. Women with a longer history of comorbidity or who took medications for the comorbidity were more likely to report the condition. Hazard ratios for all-cause mortality were not consistently affected by source of comorbidity information; the hazard ratio was lower for diabetes, but higher for the other comorbidities when medical record versus self-report was used. Model fit was better when the medical record versus self-reported data were used.Comorbidities are increasingly recognized to influence the survival of patients with breast or other cancers. Potential effects of misclassification of comorbidity status should be considered in the interpretation of research results.

  View details for DOI 10.1007/s10552-016-0715-8

  View details for PubMedID 26797455

• DISPARITIES AND DISCRIMINATION IN BREAST CANCER CARE AND QUALITY OF LIFE Gonzales, F., Shariff-Marco, S., Dwyer, L., Nuru-Jeter, A., Langer, M., Reeve, B., Taplin, S., Kurian, A., Lin-Gomez, S. OXFORD UNIV PRESS INC. 2016: S52

  View details for Web of Science ID 000526998300201

• Genetics of triple-negative breast cancer: Implications for patient care CURRENT PROBLEMS IN CANCER Afghahi, A., Telli, M. L., Kurian, A. W. 2016; 40 (2-4): 130-140

  Abstract

  Patients with triple-negative breast cancer (TNBC), defined as lacking expression of the estrogen and progesterone receptors (ER/PR) and amplification of the HER2 oncogene, often have a more aggressive disease course than do patients with hormone receptor-positive breast cancer, including higher rates of visceral and central nervous system metastases, early cancer recurrences and deaths. Triple-negative breast cancer is associated with a young age at diagnosis and both African and Ashkenazi Jewish ancestry, the latter due to three common founder mutations in the highly penetrant cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2). In the past decade, there has been a surge both in genetic testing technology and in patient access to such testing. Advances in genetic testing have enabled more rapid and less expensive commercial sequencing than could be imagined only a few years ago. Massively parallel, next-generation sequencing allows the simultaneous analysis of many different genes. Studies of TNBC patients in the current era have revealed associations of TNBC with mutations in several moderate penetrance breast cancer susceptibility genes, including PALB2, BARD1, BRIP1, RAD51C and RAD51D. Interestingly, many of these genes, like BRCA1/2, are involved in homologous recombination DNA double-stranded repair. In this review, we summarize the current understanding of pathogenic germline gene mutations associated with TNBC and the early detection and prevention strategies for women at risk of developing this high-risk breast cancer subtype. Furthermore, we discuss recent the advances in targeted therapies for TNBC patients with a hereditary predisposition, including the role of poly (ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2 mutation-associated breast cancers.

  View details for DOI 10.1016/j.currproblcancer.2016.09.007

  View details for Web of Science ID 000390980500005

• Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Daly, M. B., Pilarski, R., Axilbund, J. E., Berry, M., Buys, S. S., Crawford, B., Farmer, M., Friedman, S., Garber, J. E., Khan, S., Klein, C., Kohlmann, W., Kurian, A., Litton, J. K., Madlensky, L., Marcom, P. K., Merajver, S. D., Offit, K., Pal, T., Rana, H., Reiser, G., Robson, M. E., Shannon, K. M., Swisher, E., Voian, N. C., Weitzel, J. N., Whelan, A., Wick, M. J., Wiesner, G. L., Dwyer, M., Kumar, R., Darlow, S. 2016; 14 (2): 153-162

  Abstract

  The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer.

  View details for Web of Science ID 000369634300006

• Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries JOURNAL OF MEDICAL GENETICS Kwong, A., Shin, V. Y., Ho, J. C., Kang, E., Nakamura, S., Teo, S., Lee, A. S., Sng, J., Ginsburg, O. M., Kurian, A. W., Weitzel, J. N., Siu, M., Law, F. B., Chan, T., Narod, S. A., Ford, J. M., Ma, E. S., Kim, S. 2016; 53 (1): 15-23

  Abstract

  Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer.

  View details for DOI 10.1136/jmedgenet-2015-103132

  View details for PubMedID 26187060

• Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study Lincoln, S., Kurian, A. W., Desmond, A., et al 2016
• Association of ovarian cancer risk with mutations detected by multiple-gene germline sequencing in 95,561 women. American Society of Clinical Oncology Annual Meeting Kurian, A. W., Hughes, E., Handorf, E., et al 2016
• Compliance with guidelines and factors associated with ordering the 21-gene breast cancer assay. American Society of Clinical Oncology Annual Meeting Petkov, V., Howlader, N., Cronin, K., Kurian, A. W., Penberthy, L. 2016
• Magnitude of invasive breast cancer risk associated with mutations detected by multiple-gene germline sequencing in 95,561 women. American Society of Clinical Oncology Annual Meeting Hall, M., Hughes, E., Handorf, E., Gutin, A., Allen, B., Hartman, A., Kurian, A. W. 2016
• Clinical use of the 21-gene assay and patient experiences in early-stage breast cancer. American Society of Clinical Oncology Annual Meeting Katz, S., Friese, C., Li, Y., Deapen, D., Hamilton, A., Ward, K., Kurian, A. W. 2016
• Higher peripheral lymphocyte count to predict survival in triple-negative breast cancer American Society of Clinical Oncology Annual Meeting Afghahi, A., Rigdon, J., Purington, N., Desai, M., Pierson, E., Mathur, M., Thompson, C., Curtis, C., West, R., Horst, K., Sledge, G., Kurian, A. W. 2016
• Dissemination of 21-gene assay testing among female breast cancer patients in the US. American Society of Clinical Oncology Annual Meeting Cronin, K., Petkov, V., Howlader, N., Howe, W., Schussler, N., Kurian, A. W., Penberthy, L. 2016
• Relationship between rising bilateral mastectomy rates and increased use of neoadjuvant chemotherapy in California, 1998-2012. American Society of Clinical Oncology Annual Meeting Wapnir, I. L., Kurian, A. W., Lichtensztajn, D. Y., et al 2016
• Optimizing the Threshold for Genetic Testing for Colorectal Cancer Syndromes Naghi, L., Spector, K., Haisman, J., Kurian, A. W., et al 2016: S160
• Breast oncology precision medicine: Genomic testing and treatment at the population level. American Society of Clinical Oncology Annual Meeting Friese, C., Li, Y., Kurian, A. W., Katz, S. J. 2016
• Recurrence risk perception and quality of life after treatment of breast cancer American Society of Clinical Oncology Annual Meeting Hawley, S., Janz, N., Jagsi, R., Griffith, K., Friese, C., Kurian, A. W., et al 2016
• Prevalence and predictors of second opinions from medical oncologists for early-stage breast cancer: Results from the iCanCare study. American Society of Clinical Oncology Annual Meeting Kurian, A. W., Friese, C. R., Bondarenko, I. V., et al 2016
• Interim analysis of multiplex gene panel testing for inherited susceptibility to breast cancer San Antonio Breast Cancer Symposium Idos, G., Kurian, A. W., McDonnell, K. J., et al 2016
• The patient experience in a prospective trial of multiplex gene panel testing for cancer risk San Antonio Breast Cancer Symposium Kurian, A. W., Idos, G., McDonnell, K., et al 2016
• Yield of multiplex panel testing compared to expert opinion and validated prediction models. American Society of Clinical Oncology Annual Meeting Idos, G., Kurian, A. W., Ricker, C., et al 2016
• Determinants of Patient Choice of Health Care Providers for Breast Cancer Treatment Rai, A., Thompson, C., Kurian, A. W., Luft, H. S. 2016: 174–75
• Association of non-melanoma skin cancer with second non-cutaneous malignancy in the Women's Health Initiative. The British journal of dermatology Ransohoff, K. J., Stefanick, M. L., Li, S. n., Kurian, A. W., Wakelee, H. n., Wang, A. n., Paskett, E. n., Han, J. n., Tang, J. Y. 2016

  Abstract

  Non-melanoma skin cancer (NMSC), the most prevalent cancer in the US,(1) has been associated with increased risk of non-cutaneous malignancies, including breast cancer, lung cancer, and lymphoma. (2-7) In the Women's Health Initiative (WHI) Observational Study (OS), women with NMSC history at baseline were more likely to report history of another cancer (Odds ratio [OR] = 2.3, 95% CI = 2.18 -2.44.(6) Subsequently, Nurses Health Study (NHS) prospective analyses found increased risk of developing breast cancer, lung cancer, and melanoma in women with NMSC.(7) We sought to replicate these prospective findings in the large WHI cohort, for which important potential confounders, e.g. smoking and body mass index, and rich phenotypic data are available. This article is protected by copyright. All rights reserved.

  View details for PubMedID 27229371

• Reply to S.M. Sorscher and A.B. Hafeez Bhatti. Journal of clinical oncology Jagsi, R., Griffith, K. A., Kurian, A. W., Morrow, M., Hamilton, A. S., Graff, J. J., Katz, S. J., Hawley, S. T. 2015; 33 (35): 4233-?

  View details for DOI 10.1200/JCO.2015.63.5524

  View details for PubMedID 26371137

• Intersection of Race/Ethnicity and Socioeconomic Status in Mortality After Breast Cancer JOURNAL OF COMMUNITY HEALTH Shariff-Marco, S., Yang, J., John, E. M., Kurian, A. W., Cheng, I., Leung, R., Koo, J., Monroe, K. R., Henderson, B. E., Bernstein, L., Lu, Y., Kwan, M. L., Sposto, R., Vigen, C. L., Wu, A. H., Keegan, T. H., Gomez, S. L. 2015; 40 (6): 1287-1299

  Abstract

  We investigated social disparities in breast cancer (BC) mortality, leveraging data from the California Breast Cancer Survivorship Consortium. The associations of race/ethnicity, education, and neighborhood SES (nSES) with all-cause and BC-specific mortality were assessed among 9372 women with BC (diagnosed 1993-2007 in California with follow-up through 2010) from four racial/ethnic groups [African American, Asian American, Latina, and non-Latina (NL) White] using Cox proportional hazards models. Compared to NL White women with high-education/high-nSES, higher all-cause mortality was observed among NL White women with high-education/low-nSES [hazard ratio (HR) (95 % confidence interval) 1.24 (1.08-1.43)], and African American women with low-nSES, regardless of education [high education HR 1.24 (1.03-1.49); low-education HR 1.19 (0.99-1.44)]. Latina women with low-education/high-nSES had lower all-cause mortality [HR 0.70 (0.54-0.90)] and non-significant lower mortality was observed for Asian American women, regardless of their education and nSES. Similar patterns were seen for BC-specific mortality. Individual- and neighborhood-level measures of SES interact with race/ethnicity to impact mortality after BC diagnosis. Considering the joint impacts of these social factors may offer insights to understanding inequalities by multiple social determinants of health.

  View details for DOI 10.1007/s10900-015-0052-y

  View details for PubMedID 26072260

• Navigating choices when applying multiple imputation in the presence of multi-level categorical interaction effects STATISTICAL METHODOLOGY Mitani, A. A., Kurian, A. W., Das, A. K., Desai, M. 2015; 27: 82-99

  View details for DOI 10.1016/j.stamet.2015.06.001

  View details for Web of Science ID 000361262400006

• Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment JAMA ONCOLOGY Desmond, A., Kurian, A., Gabree, M., Mills, M. A., Anderson, M. J., Kobayashi, Y., Horick, N., Yang, S., Shannon, K. M., Tung, N., Ford, J., Lincoln, S. E., Ellisen, L. 2015; 1 (7): 943-951

  Abstract

  The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown.To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort.Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations.We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals.We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history.Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients.In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.

  View details for DOI 10.1001/jamaoncol.2015.2690

  View details for Web of Science ID 000383675900013

• "The GI Gap" in Genetic Testing for Inherited Susceptibility to Cancer Idos, G., Kurian, A. W., McDonnell, K., Ricker, C., Sturgeon, D., Culver, J., Lowstuter, K., Hartman, A., Allen, B., Teeter, C., Kingham, K., Koff, R., Lebensohn, A., Chun, N., Mills, M., Petrovchich, I., Hong, C., Ladabaum, U., Ford, J., Gruber, S. NATURE PUBLISHING GROUP. 2015: S606–S607

  View details for Web of Science ID 000363715903015

• A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients JOURNAL OF MOLECULAR DIAGNOSTICS Lincoln, S. E., Kobayashi, Y., Anderson, M. J., Yang, S., Desmond, A. J., Mills, M. A., Nilsen, G. B., Jacobs, K. B., Monzon, F. A., Kurian, A. W., Ford, J. M., Ellisen, L. W. 2015; 17 (5): 533-544

  Abstract

  Gene panels for hereditary breast and ovarian cancer risk assessment are gaining acceptance, even though the clinical utility of these panels is not yet fully defined. Technical questions remain, however, about the performance and clinical interpretation of gene panels in comparison with traditional tests. We tested 1105 individuals using a 29-gene next-generation sequencing panel and observed 100% analytical concordance with traditional and reference data on >750 comparable variants. These 750 variants included technically challenging classes of sequence and copy number variation that together represent a significant fraction (13.4%) of the pathogenic variants observed. For BRCA1 and BRCA2, we also compared variant interpretations in traditional reports to those produced using only non-proprietary resources and following criteria based on recent (2015) guidelines. We observed 99.8% net report concordance, albeit with a slightly higher variant of uncertain significance rate. In 4.5% of BRCA-negative cases, we uncovered pathogenic variants in other genes, which appear clinically relevant. Previously unseen variants requiring interpretation accumulated rapidly, even after 1000 individuals had been tested. We conclude that next-generation sequencing panel testing can provide results highly comparable to traditional testing and can uncover potentially actionable findings that may be otherwise missed. Challenges remain for the broad adoption of panel tests, some of which will be addressed by the accumulation of large public databases of annotated clinical variants.

  View details for DOI 10.1016/j.jmoldx.2015.04.009

  View details for PubMedID 26207792

• Precision Medicine in Breast Cancer Care: An Early Glimpse of Impact. JAMA oncology Kurian, A. W., Friese, C. R. 2015

  View details for DOI 10.1001/jamaoncol.2015.2719

  View details for PubMedID 26313021

• Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer BREAST CANCER RESEARCH Afghahi, A., Forgo, E., Mitani, A. A., Desai, M., Varma, S., Seto, T., Rigdon, J., Jensen, K. C., Troxell, M. L., Gomez, S. L., Das, A. K., Beck, A. H., Kurian, A. W., West, R. B. 2015; 17

  Abstract

  Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment.We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS.We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013).CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross-sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS.

  View details for DOI 10.1186/s13058-015-0623-y

  View details for Web of Science ID 000359348400001

  View details for PubMedID 26265211

  View details for PubMedCentralID PMC4534146

• Contribution of the Neighborhood Environment and Obesity to Breast Cancer Survival: The California Breast Cancer Survivorship Consortium CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Cheng, I., Shariff-Marco, S., Koo, J., Monroe, K. R., Yang, J., John, E. M., Kurian, A. W., Kwan, M. L., Henderson, B. E., Bernstein, L., Lu, Y., Sposto, R., Vigen, C., Wu, A. H., Gomez, S. L., Keegan, T. H. 2015; 24 (8): 1282-1290

  Abstract

  Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina White women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity, and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding (Quartile 4 (Q4) vs. Q1: Odds Ratio (OR)=3.24; 95% Confidence Interval (CI): 1.50-7.00); breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: Hazard Ratio (HR)=0.46; 95% CI: 0.25-0.85) and positively associated with multi-family housing (Q3 vs. Q1: HR=1.98; 95% CI: 1.20-3.26). For non-Latina Whites, lower neighborhood socioeconomic status (SES) was associated with obesity (Quintile 1 (Q1) vs. Q5: OR=2.52; 95% CI: 1.31-4.84), breast cancer-specific (Q1 vs. Q5: HR=2.75; 95% CI: 1.47-5.12), and all-cause (Q1 vs. Q5: HR=1.75; 95% CI: 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups.

  View details for DOI 10.1158/1055-9965.EPI-15-0055

  View details for PubMedID 26063477

• Treatment Decision Making and Genetic Testing for Breast Cancer: Mainstreaming Mutations. JAMA Katz, S. J., Kurian, A. W., Morrow, M. 2015

  View details for DOI 10.1001/jama.2015.8088

  View details for PubMedID 26203642

• Breast Cancer Mortality in African-American and Non-Hispanic White Women by Molecular Subtype and Stage at Diagnosis: A Population-Based Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Tao, L., Gomez, S. L., Keegan, T. H., Kurian, A. W., Clarke, C. A. 2015; 24 (7): 1039-1045

  Abstract

  Higher breast cancer mortality rates for African-American than non-Hispanic white women are well documented; however, it remains uncertain if this disparity occurs in disease subgroups defined by tumor molecular markers and stage at diagnosis. We examined racial differences in outcome according to subtype and stage in a diverse, population-based series of 103,498 patients.We obtained data for all invasive breast cancers diagnosed 1/1/2005-12/31/2012 and followed through 12/31/2012 among 93,760 non-Hispanic white and 9,738 African-American women in California. Molecular subtypes were categorized according to tumor expression of hormone receptor (HR, based on estrogen and progesterone receptors) and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer-specific mortality.After adjustment for patient, tumor and treatment characteristics, outcomes were comparable by race for Stage I or IV cancer regardless of subtype, and HR+/HER2+ or HR-/HER2+ cancer regardless of stage. We found substantially higher hazards of breast cancer death among African-American women with Stage II/III HR+/HER2- (HR, 1.31, 95% CI, 1.03-1.65, and HR, 1.39, 95% CI, 1.10-1.75, respectively) and Stage III triple-negative cancers relative to whites.There are substantial racial/ethnic disparities among patients with Stages II/III HR+/HER2- and Stage III triple-negative breast cancers but not for other subtype and stage.These data provide insights to assess barriers to targeted treatment (e.g. trastuzumab or endocrine therapy) of particular subtypes of breast cancer among African-American patients.

  View details for DOI 10.1158/1055-9965.EPI-15-0243

  View details for PubMedID 25969506

• Breast Cancer Risk Reduction, Version 2.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Bevers, T. B., Ward, J. H., Arun, B. K., Colditz, G. A., Cowan, K. H., Daly, M. B., Garber, J. E., Gemignani, M. L., Gradishar, W. J., Jordan, J. A., Korde, L. A., Kounalakis, N., Krontiras, H., Kumar, S., Kurian, A., Laronga, C., Layman, R. M., Loftus, L. S., Mahoney, M. C., Merajver, S. D., Meszoely, I. M., Mortimer, J., Newman, L., Pritchard, E., Pruthi, S., Seewaldt, V., Specht, M. C., Visvanathan, K., Wallace, A., Bergman, M. A., Kumar, R. 2015; 13 (7): 880-915

  Abstract

  Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.

  View details for Web of Science ID 000357901600008

  View details for PubMedID 26150582

• History of Recreational Physical Activity and Survival After Breast Cancer The California Breast Cancer Survivorship Consortium AMERICAN JOURNAL OF EPIDEMIOLOGY Lu, Y., John, E. M., Sullivan-Halley, J., Vigen, C., Gomez, S. L., Kwan, M. L., Caan, B. J., Lee, V. S., Roh, J. M., Shariff-Marco, S., Keegan, T. H., Kurian, A. W., Monroe, K. R., Cheng, I., Sposto, R., Wu, A. H., Bernstein, L. 2015; 181 (12): 944-955

  Abstract

  Recent epidemiologic evidence suggests that prediagnosis physical activity is associated with survival in women diagnosed with breast cancer. However, few data exist for racial/ethnic groups other than non-Latina whites. To examine the association between prediagnosis recreational physical activity and mortality by race/ethnicity, we pooled data from the California Breast Cancer Survivorship Consortium for 3 population-based case-control studies of breast cancer patients (n = 4,608) diagnosed from 1994 to 2002 and followed up through 2010. Cox proportional hazards models provided estimates of the relative hazard ratio for mortality from all causes, breast cancer, and causes other than breast cancer associated with recent recreational physical activity (i.e., in the 10 years before diagnosis). Among 1,347 ascertained deaths, 826 (61%) were from breast cancer. Compared with women with the lowest level of recent recreational physical activity, those with the highest level had a marginally decreased risk of all-cause mortality (hazard ratio = 0.88, 95% confidence interval: 0.76, 1.01) and a statistically significant decreased risk of mortality from causes other than breast cancer (hazard ratio = 0.63, 95% confidence interval: 0.49, 0.80), and particularly from cardiovascular disease. No association was observed for breast cancer-specific mortality. These risk patterns did not differ by race/ethnicity (non-Latina white, African American, Latina, and Asian American). Our findings suggest that physical activity is beneficial for overall survival regardless of race/ethnicity.

  View details for DOI 10.1093/aje/kwu466

  View details for Web of Science ID 000356180600004

  View details for PubMedID 25925388

• Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105 JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Jensen, K. C., Vinayak, S., Kurian, A. W., Lipson, J. A., Flaherty, P. J., Timms, K., Abkevich, V., Schackmann, E. A., Wapnir, I. L., Carlson, R. W., Chang, P., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B., Dakhil, S. R., Reid, J. E., Hartman, A., Manola, J., Ford, J. M. 2015; 33 (17): 1895-U57

  Abstract

  This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor-negative (≤ 5%), progesterone receptor-negative (≤ 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

  View details for DOI 10.1200/JCO.2014.57.0085

  View details for Web of Science ID 000355999800009

  View details for PubMedID 25847929

• Multigene Panel Testing in Oncology Practice: How Should We Respond? JAMA oncology Kurian, A. W., Ford, J. M. 2015; 1 (3): 277-278

  View details for DOI 10.1001/jamaoncol.2015.28

  View details for PubMedID 26181167

• Statin use and all-cancer mortality: Prospective results from the Women's Health Initiative Wang, A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Chlebowski, R. T., Simon, M. S., Desai, P. M., Wassertheil-Smoller, S., Liu, S., Kritchevsky, S., Wakelee, H. A., Stefanick, M. L. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036900373

• Clinical impact of multi-gene panel testing for hereditary breast and ovarian cancer risk assessment Ellisen, L. W., Kurian, A. W., Desmond, A. J., Mills, M., Lincoln, S. E., Shannon, K. M., Gabree, M., Tung, N. M., Ford, J. M. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for DOI 10.1200/jco.2015.33.15_suppl.1513

  View details for Web of Science ID 000358036900380

• Lymphopenia after adjuvant radiotherapy (RT) to predict poor survival in triple-negative breast cancer (TNBC). Afghahi, A., Mathur, M., Seto, T., Desai, M., Kenkare, P., Horst, K. C., Das, A. K., Thompson, C. A., Luft, H. S., Yu, P., Gomez, S., Low, Y., Shah, N. H., Kurian, A. W., Sledge, G. W. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036900228

• Concerns about cancer risk and experiences with genetic testing in a diverse population of patients with breast cancer. Journal of clinical oncology Jagsi, R., Griffith, K. A., Kurian, A. W., Morrow, M., Hamilton, A. S., Graff, J. J., Katz, S. J., Hawley, S. T. 2015; 33 (14): 1584-1591

  Abstract

  To evaluate preferences for and experiences with genetic testing in a diverse cohort of patients with breast cancer identified through population-based registries, with attention to differences by race/ethnicity.We surveyed women diagnosed with nonmetastatic breast cancer from 2005 to 2007, as reported to the SEER registries of metropolitan Los Angeles and Detroit, about experiences with hereditary risk evaluation. Multivariable models evaluated correlates of a strong desire for genetic testing, unmet need for discussion with a health care professional, and receipt of testing.Among 1,536 patients who completed the survey, 35% expressed strong desire for genetic testing, 28% reported discussing testing with a health care professional, and 19% reported test receipt. Strong desire for testing was more common in younger women, Latinas, and those with family history. Minority patients were significantly more likely to have unmet need for discussion (failure to discuss genetic testing with a health professional when they had a strong desire for testing): odds ratios of 1.68, 2.44, and 7.39 for blacks, English-speaking Latinas, and Spanish-speaking Latinas compared with whites, respectively. Worry in the long-term survivorship period was higher among those with unmet need for discussion (48.7% v 24.9%; P <.001). Patients who received genetic testing were younger, less likely to be black, and more likely to have a family cancer history.Many patients, especially minorities, express a strong desire for genetic testing and may benefit from discussion to clarify risks. Clinicians should discuss genetic risk even with patients they perceive to be at low risk, as this may reduce worry.

  View details for DOI 10.1200/JCO.2014.58.5885

  View details for PubMedID 25847940

• Racial/Ethnic and Socioeconomic Differences in Short-Term Breast Cancer Survival Among Women in an Integrated Health System AMERICAN JOURNAL OF PUBLIC HEALTH Keegan, T. H., Kurian, A. W., Gali, K., Tao, L., Lichtensztajn, D. Y., Hershman, D. L., Habel, L. A., Caan, B. J., Gomez, S. L. 2015; 105 (5): 938-946

  Abstract

  We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment.Using electronic medical records data from Kaiser Permanente Northern California linked to data from the California Cancer Registry, we included 6262 women newly diagnosed with invasive breast cancer. We analyzed survival using multivariable Cox proportional hazards regression with follow-up through 2010.After consideration of tumor stage, subtype, comorbidity, and type of treatment received, non-Hispanic White women living in low-SES neighborhoods (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.07, 1.52) and African Americans regardless of neighborhood SES (high SES: HR = 1.44; 95% CI = 1.01, 2.07; low SES: HR = 1.88; 95% CI = 1.42, 2.50) had worse overall survival than did non-Hispanic White women living in high-SES neighborhoods. Results were similar for breast cancer-specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival.Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients. (Am J Public Health. Published online ahead of print March 19, 2015: e1-e9. doi:10.2105/AJPH.2014.302406).

  View details for DOI 10.2105/AJPH.2014.302406

  View details for Web of Science ID 000358295600037

• Clinical evaluation of multigene testing for hereditary breast and ovarian cancer Ellisen, L., Kurian, A., Lincoln, S., Desmond, A., Mills, M., Shannon, K., Gabree, M., Anderson, M., Kobayashi, Y., Monzon, F., Ford, J. AMER ASSOC CANCER RESEARCH. 2015

  View details for Web of Science ID 000356730202263

• Linking electronic health records to better understand breast cancer patient pathways within and between two health systems. EGEMS (Washington, DC) Thompson, C. A., Kurian, A. W., Luft, H. S. 2015; 3 (1): 1127

  Abstract

  In a fragmented health care system, research can be challenging when one seeks to follow cancer patients as they seek care which can continue for months or years and may reflect many physician and patient decisions. Claims data track patients, but lack clinical detail. Linking routine electronic health record (EHR) data with clinical registry data allows one to gain a more complete picture of the patient journey through a cancer care episode. However, valid analytical approaches to examining care trajectories must be longitudinal and account for the dynamic nature of what is "seen" in the EHR.The Oncoshare database combines clinical detail from the California Cancer Registry and EHR data from two large health care organizations in the same catchment area-a multisite community practice and an academic medical center-for all women treated in either organization for breast cancer from 2000 to 2012. We classified EHR encounters data according to typical periods of the cancer care episode (screening, diagnosis, treatment) and posttreatment surveillance, as well as by facility used to better characterize patterns of care for patients seen at both organizations.We identified a "treated" cohort consisting of women receiving interventions for their initial cancer diagnosis, and classified their encounters over time across multiple dimensions (type of care, provider of care, and timing of care with respect to their cancer diagnosis). Forty-three percent of the patients were treated at the academic center only, 42 percent at the community center only, and 16 percent of the patients obtained care at both health care organizations. Compared to women seen at only one organization, the last group had similar-length initial care episodes, but more frequently had multiple episodes and longer observation periods.Linking EHR data from neighboring systems can enhance our information on care trajectories, but careful consideration of the complexity of the treatment process and data generating mechanisms is necessary to make valid inferences.If analyzed as a timeline, and with careful characterization of diagnostic tests, surgical interventions, and type and frequency of physician encounters, the pathways taken by women through their breast cancer episode may lead to better understanding of patient decisions.

  View details for DOI 10.13063/2327-9214.1127

  View details for PubMedID 25992389

  View details for PubMedCentralID PMC4435001

• Diabetes and Other Comorbidities in Breast Cancer Survival by Race/Ethnicity: The California Breast Cancer Survivorship Consortium (CBCSC). Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Wu, A. H., Kurian, A. W., Kwan, M. L., John, E. M., Lu, Y., Keegan, T. H., Gomez, S. L., Cheng, I., Shariff-Marco, S., Caan, B. J., Lee, V. S., Sullivan-Halley, J., Tseng, C., Bernstein, L., Sposto, R., Vigen, C. 2015; 24 (2): 361-368

  Abstract

  Background:The role of comorbidities in survival of breast cancer patients has not been well studied, particularly in non-white populations. Methods:We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated hazards ratios (HR) and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction (MI). Results:Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR=1.48, 95% CI=1.18, 1.87) or MI (HR=1.94, 95% CI=1.27-2.97). Risk patterns were similar across race/ethnicity (non-Latina White, Latina, African American and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiation nor chemotherapy (HR=2.11, 95% CI=1.32-3.36); no increased risk was observed among those who received both treatments (HR=1.13, 95% CI= 0.70-1.84) (P interaction= 0.03). A similar pattern was found for MI by radiation and chemotherapy (P interaction=0.09). Conclusion:These results may inform future treatment guidelines for breast cancer patients with a history of diabetes or MI. Impact:Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome.

  View details for DOI 10.1158/1055-9965.EPI-14-1140

  View details for PubMedID 25425578

• Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment. Current opinion in obstetrics & gynecology Kurian, A. W., Kingham, K. E., Ford, J. M. 2015; 27 (1): 23-33

  Abstract

  To summarize advances in next-generation sequencing and their application to breast and gynecologic cancer risk assessment.Next-generation sequencing panels of 6-112 cancer-associated genes are increasingly used in patient care. Studies report a 4-16% prevalence of mutations other than BRCA1/2 among patients who meet evidence-based practice guidelines for BRCA1/2 testing, with a high rate (15-88%) of uninterpretable variants of uncertain significance. Despite uncertainty about results interpretation and communication, there is early evidence of a benefit from multiple-gene sequencing panels for appropriately selected patients.Multiple-gene sequencing panels appear highly promising for the assessment of breast and gynecologic cancer risk, and they may usefully be administered in the context of cancer genetics expertise and/or clinical research protocols.

  View details for DOI 10.1097/GCO.0000000000000141

  View details for PubMedID 25502425

• How can we best respect patient autonomy in breast cancer treatment decisions? Breast cancer management Martinez, K. A., Kurian, A. W., Hawley, S. T., Jagsi, R. 2015; 4 (1): 53-64

  Abstract

  Helping patients to maximize their autonomy in breast cancer decision-making is an important aspect of patient-centered care. Shared decision-making is a strategy that aims to maximize patient autonomy by integrating the values and preferences of the patient with the biomedical expertise of the physician. Application of this approach in breast cancer decision-making has not been uniform across cancer-specific interventions (e.g., surgery, chemotherapy), and in some circumstances may present challenges to evidence-based care delivery. Increasingly precise estimates of individual patients' risk of recurrence and commensurate predicted benefit from certain therapies hold significant promise in helping patients exercise autonomous decision-making for their breast cancer care, yet will also likely complicate decision-making for certain subgroups of patients.

  View details for PubMedID 25733982

• Clinical actionability of multi-gene panel tests for hereditary breast and ovarian cancer Montreal Hereditary Breast Ovarian Cancer Meeting Ellisen, L., Lincoln, S., Kurian, A. W., et al 2015
• Addressing lack of US insurance coverage of Cancer Hereditary Multiplex Testing American Society of Clinical Oncology Annual Meeting Trosman, J., Weldon, C., Kurian, A. W., Douglas, M., et al 2015
• Prevalence and consequences of second opinions from medical oncologists for early-stage breast cancer: Results from the iCanCare study. American Society of Clinical Oncology Annual Meeting Kurian, A. W., Friese, C. R., Bondarenko, I. V., et al 2015
• Clinical impact of multi-gene panel testing for hereditary breast and ovarian cancer risk assessment. American Society of Clinical Oncology Annual Meeting Ellisen, L., Kurian, A. W., Desmond, A. J., et al 2015
• Lymphopenia after adjuvant radiotherapy to predict poor survival in triple-negative breast cancer American Society of Clinical Oncology Annual Meeting Afghahi, A., Mathur, M., Seto, T., Desai, M., Kenkare, P., Horst, K., Das, A., Thompson, C., Luft, H., Yu, P., Sledge, G., Kurian, A. W. 2015
• Statin use and all-cancer mortality: Prospective results from the Women’s Health Initiative. American Society of Clinical Oncology Annual Meeting Wang, A., Aragaki, A., Tang, J., Kurian, A. W., et al 2015
• Technical evaluation of multigene testing for hereditary breast and ovarian cancer San Antonio Breast Cancer Symposium Lincoln, S. E., Kurian, A. W., Desmond, A., et al 2015
• Concerns about cancer risk and experiences with genetic testing in a diverse population of patients with breast cancer American Society of Clinical Oncology Annual Meeting Jagsi, R., Griffith, K., Kurian, A. W., et al 2015: 1584
• Percent of Breast Cancers Positive for HER2 Varies By Ethnicity and Social Determinants of Health in California-Implications of Patient Demographics on Laboratory Benchmarks Carneal, E., Lichtensztajn, D., Clarke, C., Gomez, S., Jensen, K., Kurian, A. W., Allison, K. 2015: 37A
• Multiple-Gene Panels and the Future of Genetic Testing Current Breast Cancer Reports Kurian, A. W., Ford, J. M. 2015

  View details for DOI 10.1007/s12609-015-0181-4

• Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 1.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Daly, M. B., Pilarski, R., Axilbund, J. E., Buys, S. S., Crawford, B., Friedman, S., Garber, J. E., Horton, C., Kaklamani, V., Klein, C., Kohlmann, W., Kurian, A., Litton, J., Madlensky, L., Marcom, P. K., Merajver, S. D., Offit, K., Pal, T., Pasche, B., Reiser, G., Shannon, K. M., Swisher, E., Voian, N. C., Weitzel, J. N., Whelan, A., Wiesner, G. L., Dwyer, M. A., Kumar, R. 2014; 12 (9): 1326-1338

  Abstract

  During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome.

  View details for Web of Science ID 000341349900011

  View details for PubMedID 25190698

• Breast Density Categorization Creep Response RADIOLOGY Price, E. R., Hargreaves, J., Lipson, J. A., Sickles, E. A., Brenner, J., Lindfors, K. K., Joe, B. N., Leung, J. T., Feig, S. A., Ojeda-Fournier, H., Kurian, L. W., Love, E., Ryan, L., Ikeda, D. M. 2014; 271 (3): 927–28

  View details for Web of Science ID 000336894600041

  View details for PubMedID 24687721

• Chromosomal copy number alterations (CNAs) for risk assessment of ductal carcinoma in situ (DCIS) Afghahi, A., Forgo, E., Mitani, A., Desai, M., Varma, S., Seto, T., Jensen, K. C., Gomez, S., Das, A. K., Beck, A. H., Kurian, A. W., West, R. B. AMER SOC CLINICAL ONCOLOGY. 2014

  View details for Web of Science ID 000358613202339

• Use of the 21-gene recurrence score assay (RS) and chemotherapy (CT) across health care (HC) systems. Afghahi, A., Mitani, A., Desai, M., Yu, P., De Bruin, M. A., Seto, T., Olson, C., Kenkare, P., Gomez, S., Das, A. K., Luft, H. S., Sing, A. P., Kurian, A. W. AMER SOC CLINICAL ONCOLOGY. 2014

  View details for DOI 10.1200/jco.2014.32.15_suppl.6580

  View details for Web of Science ID 000358613203765

• Breast cancer treatment across health care systems: linking electronic medical records and state registry data to enable outcomes research. Cancer Kurian, A. W., Mitani, A., Desai, M., Yu, P. P., Seto, T., Weber, S. C., Olson, C., Kenkare, P., Gomez, S. L., de Bruin, M. A., Horst, K., Belkora, J., May, S. G., Frosch, D. L., Blayney, D. W., Luft, H. S., Das, A. K. 2014; 120 (1): 103-111

  Abstract

  Understanding of cancer outcomes is limited by data fragmentation. In the current study, the authors analyzed the information yielded by integrating breast cancer data from 3 sources: electronic medical records (EMRs) from 2 health care systems and the state registry.Diagnostic test and treatment data were extracted from the EMRs of all patients with breast cancer treated between 2000 and 2010 in 2 independent California institutions: a community-based practice (Palo Alto Medical Foundation; "Community") and an academic medical center (Stanford University; "University"). The authors incorporated records from the population-based California Cancer Registry and then linked EMR-California Cancer Registry data sets of Community and University patients.The authors initially identified 8210 University patients and 5770 Community patients; linked data sets revealed a 16% patient overlap, yielding 12,109 unique patients. The percentage of all Community patients, but not University patients, treated at both institutions increased with worsening cancer prognostic factors. Before linking the data sets, Community patients appeared to receive less intervention than University patients (mastectomy: 37.6% vs 43.2%; chemotherapy: 35% vs 41.7%; magnetic resonance imaging: 10% vs 29.3%; and genetic testing: 2.5% vs 9.2%). Linked Community and University data sets revealed that patients treated at both institutions received substantially more interventions (mastectomy: 55.8%; chemotherapy: 47.2%; magnetic resonance imaging: 38.9%; and genetic testing: 10.9% [P < .001 for each 3-way institutional comparison]).Data linkage identified 16% of patients who were treated in 2 health care systems and who, despite comparable prognostic factors, received far more intensive treatment than others. By integrating complementary data from EMRs and population-based registries, a more comprehensive understanding of breast cancer care and factors that drive treatment use was obtained.

  View details for DOI 10.1002/cncr.28395

  View details for PubMedID 24101577

  View details for PubMedCentralID PMC3867595

• HER2 Positive Rates Vary by County and Geographic Region in California Independent of Stage and Age at Presentation Allison, K. H., Jensen, K. C., Dur, C. C., Gomez, S. L., West, R. W., Kurian, A. W. 2014: 34A–35A
• Beyond barriers: fundamental 'disconnects' underlying the treatment of breast cancer patients' sexual health CULTURE HEALTH & SEXUALITY Halley, M. C., May, S. G., Rendle, K. A., Frosch, D. L., Kurian, A. W. 2014; 16 (9): 1169-1180

  Abstract

  Sexual health concerns represent one of the most frequently experienced and longest-lasting effects of breast cancer treatment, but research suggests that service providers rarely discuss sexual health with their patients. Existing research examining barriers to addressing patients' sexual health concerns has focused on discrete characteristics of the provider-patient interaction without considering the broader context in which these interactions occur. Drawing on the experiences of 21 breast cancer survivors, this paper explores three ways in which fundamental cultural and structural characteristics of the cancer care system in the USA may prevent breast cancer survivors from addressing their sexual health concerns, including: (1) when patients discussed sexual health with their providers, their providers approached sexuality as primarily physical, while participants experienced complex, multidimensional sexual health concerns; (2) specialisation within cancer care services made it difficult for patients to identify the appropriate provider to address their concerns; and (3) the structure of cancer care literally disconnects patients from the healthcare system at the time when sexual side effects commonly emerged. These data suggest that addressing breast cancer survivors' sexual health concerns requires a multifaceted approach to health systems change.

  View details for DOI 10.1080/13691058.2014.939227

  View details for Web of Science ID 000342208800012

• Obesity and Mortality After Breast Cancer by Race/Ethnicity: The California Breast Cancer Survivorship Consortium AMERICAN JOURNAL OF EPIDEMIOLOGY Kwan, M. L., John, E. M., Caan, B. J., Lee, V. S., Bernstein, L., Cheng, I., Gomez, S. L., Henderson, B. E., Keegan, T. H., Kurian, A. W., Lu, Y., Monroe, K. R., Roh, J. M., Shariff-Marco, S., Sposto, R., Vigen, C., Wu, A. H. 2014; 179 (1): 95-111

  Abstract

  We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI <18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI ≥ 40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups.

  View details for DOI 10.1093/aje/kwt233

  View details for Web of Science ID 000329061100013

  View details for PubMedID 24107615

  View details for PubMedCentralID PMC3864715

• The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors associated with racial/ethnic differences in breast cancer survival CANCER CAUSES & CONTROL Wu, A. H., Gomez, S. L., Vigen, C., Kwan, M. L., Keegan, T. H., Lu, Y., Shariff-Marco, S., Monroe, K. R., Kurian, A. W., Cheng, I., Caan, B. J., Lee, V. S., Roh, J. M., Sullivan-Halley, J., Henderson, B. E., Bernstein, L., John, E. M., Sposto, R. 2013; 24 (10): 1821-1836

  Abstract

  Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95 % confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI 0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60 (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.

  View details for DOI 10.1007/s10552-013-0260-7

  View details for Web of Science ID 000324252500007

  View details for PubMedID 23864487

• A Population-Based Observational Study of First-Course Treatment and Survival for Adolescent and Young Adult Females with Breast Cancer JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY DeRouen, M. C., Gomez, S. L., Press, D. J., Tao, L., Kurian, A. W., Keegan, T. H. 2013; 2 (3): 95-103

  View details for DOI 10.1089/jayao.2013.0004

  View details for Web of Science ID 000209404500003

• PrECOG 0105: Final efficacy results from a phase II study of gemcitabine (G) and carboplatin (C) plus iniparib (BSI-201) as neoadjuvant therapy for triple-negative (TN) and BRCA1/2 mutation-associated breast cancer Telli, M. L., Jensen, K. C., Kurian, A. W., Vinayak, S., Lipson, J. A., Schackmann, E. A., Wapnir, I., Carlson, R. W., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B. B., Dakhil, S. R., Manola, J., Ford, J. M. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419600185

• Chemotherapy (CTX) treatment patterns for early-stage breast cancer (ESBC): Changing use of anthracyclines (A) Serrurier, K. M., Hwang, J., McGuire, J. P., Lichtensztajn, D., Griffin, A. C., Gomez, S., Kurian, A. W., Melisko, M. E., Rugo, H. S. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419600392

• A young woman with bilateral breast cancer: identifying a genetic cause and implications for management. Journal of the National Comprehensive Cancer Network de Bruin, M. A., Ford, J. M., Kurian, A. W. 2013; 11 (5): 512-517

  Abstract

  Breast cancer is a common manifestation of an underlying genetic susceptibility to cancer, and 5% to 10% of all breast cancers are associated with a germline mutation in a known risk allele. Detection of mutations has implications for targeted screening and prevention strategies for probands, and for genetic counseling and testing of their family members. This report presents a case involving a 35-year-old woman with no family history of breast or ovarian cancer who presented with a palpable right breast lump. Imaging revealed multiple bilateral breast masses and right axillary adenopathy, and core needle biopsies showed invasive ductal carcinoma in both the right and left breast. This report discusses the appropriate genetics evaluation for a patient with bilateral breast cancer at a young age, including testing for mutations in BRCA1 and BRCA2, followed, if negative, by consideration of testing for mutations in TP53 (Li-Fraumeni syndrome). Given the specialized counseling and testing needs of patients with Li-Fraumeni syndrome, and the implications for targeted screening strategies if a mutation is found, referral to a cancer genetics expert is strongly recommended.

  View details for PubMedID 23667202

• Male Breast Cancer: A Comparison Between BRCA Mutation Carriers and Noncarriers in Hong Kong, Southern China Kwong, A., Chau, W., Law, F. F., Kurian, A., Ford, J. M., West, D. W., Ma, E. K. SPRINGER. 2013: 72

  View details for Web of Science ID 000318174800096

• Feasibility evaluation of an online tool to guide decisions for BRCA1/2 mutation carriers FAMILIAL CANCER Schackmann, E. A., Munoz, D. F., Mills, M. A., Plevritis, S. K., Kurian, A. W. 2013; 12 (1): 65-73

  Abstract

  Women with BRCA1 or BRCA2 (BRCA1/2) mutations face difficult decisions about managing their high risks of breast and ovarian cancer. We developed an online tool to guide decisions about cancer risk reduction (available at: http://brcatool.stanford.edu ), and recruited patients and clinicians to test its feasibility. We developed questionnaires for women with BRCA1/2 mutations and clinicians involved in their care, incorporating the System Usability Scale (SUS) and the Center for Healthcare Evaluation Provider Satisfaction Questionnaire (CHCE-PSQ). We enrolled BRCA1/2 mutation carriers who were seen by local physicians or participating in a national advocacy organization, and we enrolled clinicians practicing at Stanford University and in the surrounding community. Forty BRCA1/2 mutation carriers and 16 clinicians participated. Both groups found the tool easy to use, with SUS scores of 82.5-85 on a scale of 1-100; we did not observe differences according to patient age or gene mutation. General satisfaction was high, with a mean score of 4.28 (standard deviation (SD) 0.96) for patients, and 4.38 (SD 0.89) for clinicians, on a scale of 1-5. Most patients (77.5 %) were comfortable using the tool at home. Both patients and clinicians agreed that the decision tool could improve patient-doctor encounters (mean scores 4.50 and 4.69, on a 1-5 scale). Patients and health care providers rated the decision tool highly on measures of usability and clinical relevance. These results will guide a larger study of the tool's impact on clinical decisions.

  View details for DOI 10.1007/s10689-012-9577-8

  View details for PubMedID 23086584

• Information technology interventions to improve cancer care: a report from the American Society of Clinical Oncology Quality Care Symposium JOURNAL OF ONCOLOGY PRACTICE Kurian, A. W., Edge, S. B. 2013; 9 (3): 142-144
• Evaluation of a cancer gene sequencing panel in a hereditary risk assessment clinic. ASCO Breast Cancer Symposium Kurian, A. W., Hare, E. E., Mills, M. A., et al 2013
• Epidemiology and survival patterns of triple negative breast cancer patients with or without BRCA germline mutation in Chinese Breakthrough Breast Cancer-TNBC Conference Kwong, A., Chau, W., Law, F., Chu, T., Chan, T., Kurian, A. W., et al 2013
• PrECOG 0105: Final efficacy results from a phase II study of gemcitabine and carboplatin plus iniparib (BSI-201) as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer American Society of Clinical Oncology Annual Meeting Telli, M. L., Jensen, K., Kurian, A. W., et al 2013
• Impact of California breast density notification law SB 1538 on California women and their health care providers American Association for Cancer Research Annual Meeting Ikeda, D. M., Thomas, W. R., Joe, B. N., Lindfors, K., Brenner, R. J., Feig, S., Bassett, L. W., Leung, J. W., Ojeda-Fournier, H., Hargreaves, J., Price, E., Lipson, J. A., Kurian, A. W., et al 2013
• Variation in HER2 positive rates in California by geographic region: Implications for setting pathology laboratory benchmarks San Antonio Breast Cancer Symposium Allison, K. H., Jensen, K., West, R., Clarke, C. A., Gomez, S. L., Kurian, A. W. 2013
• Beyond Barriers: Systemic Constraints Limiting Sexual Health Care for Breast Cancer Survivors Halley, M., May, S., Rendle, K., Frosch, D., Kurian, A. W. 2013: 133
• Male breast cancer: a comparison between BRCA mutation carriers and non-carriers in Hong Kong, Southern China American Society of Breast Surgeons Annual Meeting Kwong, A., Chau, W., Law, F., Kurian, A. W., et al 2013
• A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk BREAST CANCER RESEARCH AND TREATMENT Vinayak, S., Schwartz, E. J., Jensen, K., Lipson, J., Alli, B., McPherson, L., Fernandez, A. M., Sharma, V. B., Staton, A., Mills, M. A., Schackmann, E. A., Telli, M. L., Kardashian, A., Ford, J. M., Kurian, A. W. 2013; electronic publication ahead of print, October 30
• Impact of breast cancer subtypes on three-year survival among adolescent and young adult women BREAST CANCER RESEARCH Keegan, T. H., Press, D. J., Tao, L., DeRouen, M. C., Kurian, A. W., Clarke, C. A., Gomez, S. L. 2013; 15 (5): R95
• The California Breast Density Information Group: A Collaborative Response to the Issues of Breast Density, Breast Cancer Risk, and Breast Density Notification Legislation RADIOLOGY Price, E. R., Hargreaves, J., Lipson, J. A., Sickles, E. A., Brenner, R. J., Lindfors, K. K., Joe, B. N., Leung, J. W., Feig, S. A., Bassett, L. W., Daniel, B. L., Kurian, A. W., Love, E., Ryan, L., Walgenbach, D. D., Ikeda, D. M. 2013: 887–92

  Abstract

  In anticipation of breast density notification legislation in the state of California, which would require notification of women with heterogeneously and extremely dense breast tissue, a working group of breast imagers and breast cancer risk specialists was formed to provide a common response framework. The California Breast Density Information Group identified key elements and implications of the law, researching scientific evidence needed to develop a robust response. In particular, issues of risk associated with dense breast tissue, masking of cancers by dense tissue on mammograms, and the efficacy, benefits, and harms of supplementary screening tests were studied and consensus reached. National guidelines and peer-reviewed published literature were used to recommend that women with dense breast tissue at screening mammography follow supplemental screening guidelines based on breast cancer risk assessment. The goal of developing educational materials for referring clinicians and patients was reached with the construction of an easily accessible Web site that contains information about breast density, breast cancer risk assessment, and supplementary imaging. This multi-institutional, multidisciplinary approach may be useful for organizations to frame responses as similar legislation is passed across the United States. © RSNA, 2013 Online supplemental material is available for this article.

• Patterns and predictors of breast cancer chemotherapy use in Kaiser Permanente Northern California, 2004-2007 BREAST CANCER RESEARCH AND TREATMENT Kurian, A. W., Lichtensztajn, D. Y., Keegan, T. H., Leung, R. W., Shema, S. J., Hershman, D. L., Kushi, L. H., Habel, L. A., Kolevska, T., Caan, B. J., Gomez, S. L. 2013; 137 (1): 247-260

  Abstract

  Chemotherapy regimens for early stage breast cancer have been tested by randomized clinical trials, and specified by evidence-based practice guidelines. However, little is known about the translation of trial results and guidelines to clinical practice. We extracted individual-level data on chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated healthcare system serving 29 % of the local population. We linked data to the California Cancer Registry, incorporating socio-demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. Factors associated with receiving chemotherapy included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI) 1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR 11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86), Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI 2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23, 95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system, chemotherapy use followed practice guidelines, but varied by race and socio-demographic factors. These findings may inform efforts to optimize quality in breast cancer care.

  View details for DOI 10.1007/s10549-012-2329-5

  View details for Web of Science ID 000312710500023

  View details for PubMedID 23139057

• Novel BRCA1 and BRCA2 genomic rearrangements in Southern Chinese breast/ovarian cancer patients BREAST CANCER RESEARCH AND TREATMENT Kwong, A., Ng, E. K., Law, F. B., Wong, H. N., Wa, A., Wong, C. L., Kurian, A. W., West, D. W., Ford, J. M., Ma, E. S. 2012; 136 (3): 931-933

  View details for DOI 10.1007/s10549-012-2292-1

  View details for Web of Science ID 000312071000033

  View details for PubMedID 23099436

  View details for PubMedCentralID PMC3511694

• Genetic Polymorphisms as Predictors of Breast Cancer Risk CURRENT BREAST CANCER REPORTS de Bruin, M. A., Ford, J. M., Kurian, A. W. 2012; 4 (4): 232–39

  View details for DOI 10.1007/s12609-012-0091-7

  View details for Web of Science ID 000219327600002

• Identification of BRCA1/2 Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis PLOS ONE Kwong, A., Ng, E. K., Wong, C. L., Law, F. B., Au, T., Wong, H. N., Kurian, A. W., West, D. W., Ford, J. M., Ma, E. S. 2012; 7 (9)

  Abstract

  Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China.A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated.In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment.

  View details for DOI 10.1371/journal.pone.0043994

  View details for Web of Science ID 000308462000010

  View details for PubMedID 22970155

  View details for PubMedCentralID PMC3436879

• Breast cancer risk factors differ between Asian and white women with BRCA1/2 mutations FAMILIAL CANCER de Bruin, M. A., Kwong, A., Goldstein, B. A., Lipson, J. A., Ikeda, D. M., McPherson, L., Sharma, B., Kardashian, A., Schackmann, E., Kingham, K. E., Mills, M. A., West, D. W., Ford, J. M., Kurian, A. W. 2012; 11 (3): 429-439

  Abstract

  The prevalence and penetrance of BRCA1 and BRCA2 (BRCA1/2) mutations may differ between Asians and whites. We investigated BRCA1/2 mutations and cancer risk factors in a clinic-based sample. BRCA1/2 mutation carriers were enrolled from cancer genetics clinics in Hong Kong and California according to standardized entry criteria. We compared BRCA mutation position, cancer history, hormonal and reproductive exposures. We analyzed DNA samples for single-nucleotide polymorphisms reported to modify breast cancer risk. We performed logistic regression to identify independent predictors of breast cancer. Fifty Asian women and forty-nine white American women were enrolled. BRCA1 mutations were more common among whites (67 vs. 42 %, p = 0.02), and BRCA2 mutations among Asians (58 vs. 37 %, p = 0.04). More Asians had breast cancer (76 vs. 53 %, p = 0.03); more whites had relatives with breast cancer (86 vs. 50 %, p = 0.0003). More whites than Asians had breastfed (71 vs. 42 %, p = 0.005), had high BMI (median 24.3 vs. 21.2, p = 0.04), consumed alcohol (2 drinks/week vs. 0, p < 0.001), and had oophorectomy (61 vs. 34 %, p = 0.01). Asians had a higher frequency of risk-associated alleles in MAP3K1 (88 vs. 59 %, p = 0.005) and TOX3/TNRC9 (88 vs. 55 %, p = 0.0002). On logistic regression, MAP3K1 was associated with increased breast cancer risk for BRCA2, but not BRCA1 mutation carriers; breast density was associated with increased risk among Asians but not whites. We found significant differences in breast cancer risk factors between Asian and white BRCA1/2 mutation carriers. Further investigation of racial differences in BRCA1/2 mutation epidemiology could inform targeted cancer risk-reduction strategies.

  View details for DOI 10.1007/s10689-012-9531-9

  View details for PubMedID 22638769

• A Simulation Model to Predict the Impact of Prophylactic Surgery and Screening on the Life Expectancy of BRCA1 and BRCA2 Mutation Carriers CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Sigal, B. M., Munoz, D. F., Kurian, A. W., Plevritis, S. K. 2012; 21 (7): 1066-1077

  Abstract

  Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy.We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters.The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for BRCA1 and 3.4 to 4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for BRCA1 and 0.5 to 4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for BRCA1 and 1.5 to 4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy.Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted.

  View details for DOI 10.1158/1055-9965.EPI-12-0149

  View details for PubMedID 22556274

• Age-Specific Incidence of Breast Cancer Subtypes: Understanding the BlackWhite Crossover JOURNAL OF THE NATIONAL CANCER INSTITUTE Clarke, C. A., Keegan, T. H., Yang, J., Press, D. J., Kurian, A. W., Patel, A. H., Lacey, J. V. 2012; 104 (14): 1094-1101

  Abstract

  Breast cancer incidence is higher among black women than white women before age 40 years, but higher among white women than black women after age 40 years (black-white crossover). We used newly available population-based data to examine whether the age-specific incidences of breast cancer subtypes vary by race and ethnicity.We classified 91908 invasive breast cancers diagnosed in California between January 1, 2006, and December 31, 2009, by subtype based on tumor expression of estrogen receptor (ER) and progesterone receptor (PR)-together referred to as hormone receptor (HR)-and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes were classified as ER or PR positive and HER2 negative (HR(+)/HER2(-)), ER or PR positive and HER2 positive (HR(+)/HER2(+)), ER and PR negative and HER2 positive (HR(-)/HER2(+)), and ER, PR, and HER2 negative (triple-negative). We calculated and compared age-specific incidence rates, incidence rate ratios, and 95% confidence intervals by subtype and race (black, white, Hispanic, and Asian). All P values are two-sided.We did not observe an age-related black-white crossover in incidence for any molecular subtype of breast cancer. Compared with white women, black women had statistically significantly higher rates of triple-negative breast cancer at all ages but statistically significantly lower rates of HR(+)/HER2(-) breast cancers after age 35 years (all P < .05). The age-specific incidence of HR(+)/HER2(+) and HR(-)/HER2(+) subtypes did not vary markedly between white and black women.The black-white crossover in breast cancer incidence occurs only when all breast cancer subtypes are combined and relates largely to higher rates of triple-negative breast cancers and lower rates of HR(+)/HER2(-) breast cancers in black vs white women.

  View details for DOI 10.1093/jnci/djs264

  View details for Web of Science ID 000306969100011

  View details for PubMedID 22773826

  View details for PubMedCentralID PMC3640371

• Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines PLOS ONE Powell, A. A., Talasaz, A. H., Zhang, H., Coram, M. A., Reddy, A., Deng, G., Telli, M. L., Advani, R. H., Carlson, R. W., Mollick, J. A., Sheth, S., Kurian, A. W., Ford, J. M., Stockdale, F. E., Quake, S. R., Pease, R. F., Mindrinos, M. N., Bhanot, G., Dairkee, S. H., Davis, R. W., Jeffrey, S. S. 2012; 7 (5)

  Abstract

  To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy.For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery.

  View details for DOI 10.1371/journal.pone.0033788

  View details for PubMedID 22586443

• Patient, Hospital, and Neighborhood Factors Associated with Treatment of Early-Stage Breast Cancer among Asian American Women in California CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Gomez, S. L., Press, D. J., Lichtensztajn, D., Keegan, T. H., Shema, S. J., Le, G. M., Kurian, A. W. 2012; 21 (5): 821-834

  Abstract

  Clinical guidelines recommend breast-conserving surgery (BCS) with radiation as a viable alternative to mastectomy for treatment of early-stage breast cancer. Yet, Asian Americans are more likely than other groups to have mastectomy or omit radiation after BCS.We applied polytomous logistic regression and recursive partitioning to analyze factors associated with mastectomy, or BCS without radiation, among 20,987 California Asian Americans diagnosed with stage 0 to II breast cancer from 1990 to 2007.The percentage receiving mastectomy ranged from 40% among U.S.-born Chinese to 58% among foreign-born Vietnamese. Factors associated with mastectomy included tumor characteristics such as larger tumor size, patient characteristics such as older age and foreign birthplace among some Asian Americans ethnicities, and additional factors including hospital [smaller hospital size, not National Cancer Institute cancer center, low socioeconomic status (SES) patient composition, and high hospital Asian Americans patient composition] and neighborhood characteristics (ethnic enclaves of low SES). These hospital and neighborhood characteristics were also associated with BCS without radiation. Through recursive partitioning, the highest mastectomy subgroups were defined by tumor characteristics such as size and anatomic location, in combination with diagnosis year and nativity.Tumor characteristics and, secondarily, patient, hospital, and neighborhood factors are predictors of mastectomy and omission of radiation following BCS among Asian Americans.By focusing on interactions among patient, hospital, and neighborhood factors in the differential receipt of breast cancer treatment, our study identifies subgroups of interest for further study and translation into public health and patient-focused initiatives to ensure that all women are fully informed about treatment options.

  View details for DOI 10.1158/1055-9965.EPI-11-1143

  View details for Web of Science ID 000303908200017

  View details for PubMedID 22402290

  View details for PubMedCentralID PMC3406750

• Accuracy of BRCA1/2 Mutation Prediction Models for Different Ethnicities and Genders: Experience in a Southern Chinese Cohort WORLD JOURNAL OF SURGERY Kwong, A., Wong, C. H., Suen, D. T., Co, M., Kurian, A. W., West, D. W., Ford, J. M. 2012; 36 (4): 702-713

  Abstract

  BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Results are conflicting in Asian populations. Most studies did not account for gender-specific prediction. We evaluated the performance of these models in a Chinese cohort, including males, before BRCA1/2 mutation testing.The five risk models were used to calculate the probability of BRCA mutations in probands with breast and ovarian cancers; 267 were non-BRCA mutation carriers (247 females and 20 males) and 43 were BRCA mutation carriers (38 females and 5 males).Mean BRCA prediction scores for all models were statistically better for carriers than noncarriers for females but not for males. BRCAPRO overestimated the numbers of female BRCA1/2 mutation carriers at thresholds ≥20% but underestimated if <20%. BRCAPRO and BOADICEA underestimated the number of male BRCA1/2 mutation carriers whilst Myriad II underestimated the number of both male and female carriers. In females, BRCAPRO showed similar discrimination, as measured by the area under the receiver operator characteristic curve (AUC) for BRCA1/2 combined mutation prediction to BOADICEA, but performed better than BOADICEA in BRCA1 mutation prediction (AUC 93% vs. 87%). BOADICEA had the best discrimination for BRCA1/2 combined mutation prediction (AUC 87%) in males.The variation in model performance underscores the need for research on larger Asian cohorts as prediction models, and the possible need for customizing these models for different ethnic groups and genders.

  View details for DOI 10.1007/s00268-011-1406-y

  View details for Web of Science ID 000301591200002

  View details for PubMedID 22290208

  View details for PubMedCentralID PMC3299960

• Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: More Trouble With Phenocopies Reply JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Whittemore, A. S. 2012; 30 (10): 1143-1144

  View details for DOI 10.1200/JCO.2011.40.9938

  View details for Web of Science ID 000302631300026

• Occurrence of breast cancer subtypes in adolescent and young adult women BREAST CANCER RESEARCH Keegan, T. H., DeRouen, M. C., Press, D. J., Kurian, A. W., Clarke, C. A. 2012; 14 (2)

  Abstract

  Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER-/PR-/HER2-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood.Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+), and logistic regression was used to evaluate differences in subtype characteristics by age group.AYAs had higher proportions of HR+/HER2+, triple-negative and HR-/HER2+ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR+/HER2- and triple-negative subtypes in AYAs varied substantially by race/ethnicity.The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs.

  View details for DOI 10.1186/bcr3156

  View details for Web of Science ID 000304771800030

  View details for PubMedID 22452927

  View details for PubMedCentralID PMC3446389

• The impact of “significant others” on breast cancer patients’ treatment decision making. ASCO Breast Cancer Symposium May, S., Rendle, K., Halley, M., Ventre, N., Kurian, A. W., Yu, P. P. 2012
• The California Breast Cancer Survivorship Consortium: Prognostic factors associated with racial/ethnic differences in breast cancer survival American Association for Cancer Research Annual Meeting Vigen, C., Gomez, S. L., Sposto, R., Lu, Y., Kwan, M., John, E., Monroe, K., Keegan, T. H., Shariff-Marco, S., Kurian, A. W. 2012: A04
• Oncoshare: lessons learned from building an integrated multi-institutional database for comparative effectiveness research. AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium Weber, S. C., Seto, T., Olson, C., Kenkare, P., Kurian, A. W., Das, A. K. 2012; 2012: 970-978

  Abstract

  Comparative effectiveness research (CER) using observational data requires informatics methods for the extraction, standardization, sharing, and integration of data derived from a variety of electronic sources. In the Oncoshare project, we have developed such methods as part of a collaborative multi-institutional CER study of patterns, predictors, and outcome of breast cancer care. In this paper, we present an evaluation of the approaches we undertook and the lessons we learned in building and validating the Oncoshare data resource. Specifically, we determined that 1) the state or regional cancer registry makes the most efficient starting point for determining inclusion of subjects; 2) the data dictionary should be based on existing registry standards, such as Surveillance, Epidemiology and End Results (SEER), when applicable; 3) the Social Security Administration Death Master File (SSA DMF), rather than clinical resources, provides standardized ascertainment of mortality outcomes; and 4) CER database development efforts, despite the immediate availability of electronic data, may take as long as two years to produce validated, reliable data for research. Through our efforts using these methods, Oncoshare integrates complex, longitudinal data from multiple electronic medical records and registries and provides a rich, validated resource for research on oncology care.

  View details for PubMedID 23304372

• A Prospective Study of Total Gastrectomy for CDH1-Positive Hereditary Diffuse Gastric Cancer ANNALS OF SURGICAL ONCOLOGY Chen, Y., Kingham, K., Ford, J. M., Rosing, J., Van Dam, J., Jeffrey, R. B., Longacre, T. A., Chun, N., Kurian, A., Norton, J. A. 2011; 18 (9): 2594-2598

  Abstract

  Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome. Up to 30% of families with HDGC have mutations in the E-cadherin gene, CDH1. The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively.Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. Proportions were compared by Fisher's exact test, and survival by the Breslow modification of the Wilcoxon rank-sum test.Each patient underwent total gastrectomy (TG), and 17 (94%) were found to have signet ring cell adenocarcinoma. Twelve of 13 asymptomatic patients had T1, N0 cancer, and only 2/12 (16%) had it diagnosed preoperatively despite state-of-the-art screening methods. Each asymptomatic patient did well postoperatively, and no patient has recurred. For five symptomatic patients, each (100%) was found to have signet ring cell adenocarcinoma (P = 0.002 versus asymptomatic) by preoperative endoscopy; three (60%) had lymph node involvement and two (40%) had distant metastases at time of operation. Two-year survival was 100% for asymptomatic and 40% for symptomatic patients (P < 0.01).The data show that asymptomatic patients with family history of HDGC and CDH1 mutation have high probability of having signet ring cell adenocarcinoma of the stomach that is not able to be diagnosed on endoscopy; when symptoms arise, the diagnosis can be made by endoscopy, but they have metastases and decreased survival. Surveillance endoscopy is of limited value, and prophylactic gastrectomy (PG) is recommended for patients with family history of HDGC and CDH1 mutations.

  View details for DOI 10.1245/s10434-011-1648-9

  View details for PubMedID 21424370

• Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry BREAST CANCER RESEARCH AND TREATMENT Telli, M. L., Chang, E. T., Kurian, A. W., Keegan, T. H., McClure, L. A., Lichtensztajn, D., Ford, J. M., Gomez, S. L. 2011; 127 (2): 471-478

  Abstract

  The distribution of breast cancer molecular subtypes has been shown to vary by race/ethnicity, highlighting the importance of host factors in breast tumor biology. We undertook the current analysis to determine population-based distributions of breast cancer subtypes among six ethnic Asian groups in California. We defined immunohistochemical (IHC) surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese, and South Asian patients diagnosed with incident, primary, invasive breast cancer between 2002 and 2007 in the California Cancer Registry as: hormone receptor-positive (HR+)/HER2- [estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-negative (HER2-)], triple-negative (ER-, PR-, and HER2-), and HER2-positive (ER±, PR±, and HER2+). We calculated frequencies of breast cancer subtypes among Asian ethnic groups and evaluated their associations with clinical and demographic factors. Complete IHC data were available for 8,140 Asian women. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5-2.2], Filipina (OR = 1.3, 95% CI = 1.2-1.5), Vietnamese (OR = 1.3, 95% CI = 1.1-1.6), and Chinese (OR = 1.1, 95% CI = 1.0-1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. We report a significant ethnic disparity in HER2-positive breast cancer in a large population-based cohort enriched for Asian-Americans. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care.

  View details for DOI 10.1007/s10549-010-1173-8

  View details for PubMedID 20957431

• Hereditary cancer: counseling women at risk CONTEMPORARY OBSTETRICS AND GYNECOLOGY Lebensohn, A. P., Kingham, K. E., Chun, N. M., Kurian, A. W. 2011; 56 (4): 30-38
• A Time to Decide: Patient Perspectives on Breast Cancer Treatment Decision Making May, S., Rendle, K., Ventre, N., Frosch, D., Kurian, A. UNIV ALBERTA, INT INST QUALITATIVE METHODOLOGY. 2011: 456

  View details for Web of Science ID 000312744200019

• Breast Cancer Risk Factors among Asian Versus Caucasian Women with BRCA1/2 Mutations. San Antonio Breast Cancer Symposium de Bruin, M., Kwong, A., Goldstein, B. L., Lipson, J., Ikeda, D., McPherson, L., Sharma, B., Kardashian, A., Schackmann, E., Kingham, K., Mills, M. A., West, D. W., Ford, J. M., Kurian, A. W. 2011
• Utilizing BRCA1/2 mutation status to select patients for breast cancer clinical trials: Experience from a prospective phase II trial. ASCO Breast Cancer Symposium Schackmann, E. A., Vinayak, S., Kurian, A. W., et al 2011: 161
• A Phase II Study of Gemcitabine and Carboplatin Plus Iniparib (BSI-201) as Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer. San Antonio Breast Cancer Symposium Telli, M. L., Kurian, A. W., Jensen, K. C., et al 2011
• A time to decide: patient perspectives on breast cancer treatment decision making May, S., Rendle, K., Ventre, N., Kurian, A. W., Frosch, D. 2011: 456
• More than a Moment: The Role of Significant Others in Medical Decision Making May, S., Rendle, K., Ventre, N., Kurian, A. W., Frosch, D. 2011: 488–89
• High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients BREAST CANCER RESEARCH AND TREATMENT Kwong, A., Ng, E. K., Law, F. B., Wong, L. P., To, M. Y., Cheung, M. T., Wong, H. N., Chan, V. W., Kurian, A., West, D. W., Ford, J. M., Ma, E. S. 2010; 122 (2): 605-607

  View details for DOI 10.1007/s10549-010-0882-3

  View details for Web of Science ID 000278810700034

  View details for PubMedID 20396944

• Genetic/familial high-risk assessment: breast and ovarian. Journal of the National Comprehensive Cancer Network Daly, M. B., Axilbund, J. E., Buys, S., Crawford, B., Farrell, C. D., Friedman, S., Garber, J. E., Goorha, S., Gruber, S. B., Hampel, H., Kaklamani, V., Kohlmann, W., Kurian, A., Litton, J., Marcom, P. K., Nussbaum, R., Offit, K., Pal, T., Pasche, B., Pilarski, R., Reiser, G., Shannon, K. M., Smith, J. R., Swisher, E., Weitzel, J. N. 2010; 8 (5): 562-594

  View details for PubMedID 20495085

• Increasing Mastectomy Rates for Early-Stage Breast Cancer? Population-Based Trends From California JOURNAL OF CLINICAL ONCOLOGY Gomez, S. L., Lichtensztajn, D., Kurian, A. W., Telli, M. L., Chang, E. T., Keegan, T. H., Glaser, S. L., Clarke, C. A. 2010; 28 (10): E155-E157

  View details for DOI 10.1200/JCO.2009.26.1032

  View details for Web of Science ID 000276152200036

  View details for PubMedID 20159812

• BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Kurian, A. W. 2010; 22 (1): 72-78

  Abstract

  To summarize evidence on the prevalence and spectrum of BRCA1 and BRCA2 BRCA1/2 mutations across racial and ethnic groups and discuss implications for clinical practice.The prevalence of BRCA1/2 mutations is comparable among breast cancer patients of African, Asian, white, and Hispanic descent: approximately 1-4% per gene. Among ovarian cancer patients in North America, BRCA1/2 mutations are present in 13-15%. Between racial/ethnic groups, there are important differences in the spectrum of BRCA1 compared with BRCA2 mutations, in BRCA1/2 variants of uncertain significance, and in the accuracy of clinical models that predict BRCA1/2 mutation carriage.Given the significant prevalence of BRCA1/2 mutations across race/ethnicity, there is a need to expand and customize genetic counseling, genetic testing, and follow-up care for members of all racial/ethnic groups.

  View details for DOI 10.1097/GCO.0b013e328332dca3

  View details for Web of Science ID 000273934800013

  View details for PubMedID 19841585

• Lifetime risks of specific breast cancer subtypes among women in four racial/ethnic groups BREAST CANCER RESEARCH Kurian, A. W., Fish, K., Shema, S. J., Clarke, C. A. 2010; 12 (6)

  Abstract

  Breast cancer comprises clinically distinct subtypes, but most risk statistics consider breast cancer only as a single entity. To estimate subtype-specific lifetime breast cancer risks, we took advantage of population-based data for which information regarding tumor expression of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2) was newly available.We included women whose breast cancer was diagnosed in the state of California from 2006 to 2007 and was reported to the National Cancer Institute's Surveillance, Epidemiology and End Results Program (N = 40,936). We calculated absolute lifetime and age-specific probabilities (percent, 95% confidence interval) of developing breast cancer subtypes defined by ER, PR, and HER2 status - luminal (ER and/or PR-positive, HER2-negative), HER2-positive (ER and PR-positive or negative, HER2-positive), and triple-negative (ER-negative, PR-negative, and HER2-negative) - separately for white, black, Hispanic, and Asian women.The luminal breast cancer subtype predominates across racial/ethnic groups, with lifetime risk lowest in Hispanic women (4.60%, 4.41-4.80%) and highest in white women (8.10%, 7.94-8.20%). HER2-positive breast cancer varies less by race (1.56-1.91%). Lifetime risk of triple-negative breast cancer is highest in black women (1.98%, 1.80-2.17%), compared to 0.77% (0.67-0.88%) for Asians, 1.04% (0.96-1.13%) for Hispanics and 1.25% (1.20-1.30%) for whites. Across racial/ethnic groups, nearly half of all luminal breast cancers occur after age 70.These absolute risk estimates may inform health policy and resource planning across diverse populations, and can help patients and physicians weigh the probabilities of developing specific breast cancer subtypes against competing health risks.

  View details for DOI 10.1186/bcr2780

  View details for Web of Science ID 000288751500010

  View details for PubMedID 21092082

  View details for PubMedCentralID PMC3046442

• The Accuracy of BRCA1/2 Mutation Prediction Models in Different Ethnicity and Gender: Experience in a Chinese Cohort San Antonio Breast Cancer Symposium Kwong, A., Wong, C., Suen, D., Choi, C., Wong, C., Law, F., Kurian, A. W., et al 2010
• A High Percentage of Triple Negative Tumors Present as Palpable Masses San Antonio Breast Cancer Symposium Kalu, O. N., Kurian, A. W., Wapnir, I. L. 2010
• Statins May Reduce Breast Cancer Risk, Particularly Hormone Receptor-Negative Disease. Current breast cancer reports Vinayak, S., Kurian, A. W. 2009; 1 (3): 148-156

  Abstract

  Estrogen and progesterone receptor-negative breast cancer disproportionately affects young women and African Americans, has a poor prognosis, and lacks an effective chemoprevention agent. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as "statins," are appealing candidate agents for breast cancer chemoprevention because of their demonstrated safety after decades of widespread use. In preclinical studies, statins inhibit multiple cancer-associated pathways in both hormone receptor (HR)-negative and HR-positive cell lines. Epidemiologic studies of statins and breast cancer show inconsistent results, with some suggesting a reduction in HR-negative breast cancer incidence in lipophilic statin users. However, large meta-analyses show no association between statin use and overall risk of breast cancer, although most did not evaluate tumor HR status. Multiple phase 1 and 2 prevention studies of statins for breast cancer risk reduction are ongoing. If results are promising, they may justify a randomized trial of statins for breast cancer chemoprevention, with a focus on HR-negative disease.

  View details for PubMedID 22540021

• Performance of Prediction Models for BRCA Mutation Carriage in Three Racial/Ethnic Groups: Findings from the Northern California Breast Cancer Family Registry CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kurian, A. W., Gong, G. D., John, E. M., Miron, A., Felberg, A., Phipps, A. I., West, D. W., Whittemore, A. S. 2009; 18 (4): 1084-1091

  Abstract

  Patients with early-onset breast and/or ovarian cancer frequently wish to know if they inherited a mutation in one of the cancer susceptibility genes, BRCA1 or BRCA2. Accurate carrier prediction models are needed to target costly testing. Two widely used models, BRCAPRO and BOADICEA, were developed using data from non-Hispanic Whites (NHW), but their accuracies have not been evaluated in other racial/ethnic populations.We evaluated the BRCAPRO and BOADICEA models in a population-based series of African American, Hispanic, and NHW breast cancer patients tested for BRCA1 and BRCA2 mutations. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves.Both models were well-calibrated within each racial/ethnic group, with some exceptions. BOADICEA overpredicted mutations in African Americans and older NHWs, and BRCAPRO underpredicted in Hispanics. In all racial/ethnic groups, the models overpredicted in cases whose personal and family histories indicated >80% probability of carriage. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. For example, BRCAPRO's areas under the receiver operating characteristic curves were 83% (95% confidence interval, 63-93%) for NHWs, compared with 74% (59-85%) for African Americans and 58% (45-70%) for Hispanics.The poor performance of the model for Hispanics may be due to model misspecification in this racial/ethnic group. However, it may also reflect racial/ethnic differences in the distributions of personal and family histories among breast cancer cases in the Northern California population.

  View details for DOI 10.1158/1055-9965.EPI-08-1090

  View details for PubMedID 19336551

• Tailoring BRCAPRO to Asian-Americans IN REPLY JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Whittemore, A. S., Ford, J. M. 2009; 27 (4): 643–44

  View details for DOI 10.1200/JCO.2008.20.7191

  View details for Web of Science ID 000262894400031

• The Decline in Breast Cancer Incidence: Real or Imaginary? CURRENT ONCOLOGY REPORTS Kurian, A. W., Clarke, C. A., Carlson, R. W. 2009; 11 (1): 21-28

  Abstract

  Breast cancer is a major global problem, with nearly 1 million cases occurring each year. Over the past several decades, the disease's incidence has risen worldwide, increasing in developing and developed countries. This rise in breast cancer incidence has been attributed to changes in lifestyle and reproductive factors and to the dissemination of population-wide mammographic screening, which facilitates diagnosis. Recently, a decline in breast cancer incidence was reported in the United States and several other developed countries, and a substantial reduction in menopausal hormone therapy use was proposed as a possible cause. However, significant controversy remains as to the timing, causes, generalizability, and longevity of this reported decline in incidence.

  View details for Web of Science ID 000207843700006

  View details for PubMedID 19080738

• Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers FAMILIAL CANCER Staton, A. D., Kurian, A. W., Cobb, K., Mills, M. A., Ford, J. M. 2008; 7 (2): 179-186

  Abstract

  Women with mutations in the BRCA1 or BRCA2 cancer susceptibility genes face unique choices regarding management of their high risk for breast and ovarian cancer that impact their reproductive options. In order to explore women's preferences for management of elevated cancer risk, we evaluated the decisions of BRCA1/2 mutation carriers about contraception, prophylactic surgery, and family planning.An internet-based questionnaire assessing high-risk women's preferences about cancer risk management and reproductive options was designed, pilot-tested and administered electronically to 284 participants of an internet-based advocacy group for women with BRCA1/2 mutations.Two hundred and thirteen eligible participants completed the majority of the survey. Mean age was 34 years; 66% were BRCA1 mutation carriers and 34% were BRCA2 mutation carriers. Most women (92%) had used oral contraceptive pills. About 88% of responders reported frequent or extreme worry about transmitting the mutation to their children. Despite their high level of worry, few responders said they would likely consider using assisted reproduction technologies such as a pregnancy surrogate (3%), cryopreservation of oocytes or embryos (8%), or pre-implantation genetic diagnosis (PGD) to select embryos without BRCA1/2 mutations (13%).Although they expressed substantial concern about transmitting BRCA1/2 mutations to their children, only a minority of the high-risk women surveyed were likely to consider currently available assisted reproductive strategies. Further research is necessary to explore the risk management preferences of patients with inherited cancer predisposition, and to incorporate these preferences into clinical care.

  View details for DOI 10.1007/s10689-007-9171-7

  View details for PubMedID 18026853

• Magnetic resonance galactography: A feasibility study in women with prior atypical breast duct cytology BREAST JOURNAL Kurian, A. W., Hartman, A., Mills, M. A., Logan, L. J., Sawyer, A. M., Ford, J. M., Daniel, B. L. 2008; 14 (2): 211-214

  View details for Web of Science ID 000253712200022

  View details for PubMedID 18248552

• Asian race and breast cancer subtypes: a study from the California Cancer Registry American Society of Clinical Oncology Annual Meeting Telli, M. L., Kurian, A. W., Chang, E., et al 2008: 6618
• A carrier of both MEN1 and BRCA2 mutations: case report a-lid review of the literature CANCER GENETICS AND CYTOGENETICS Ghataorhe, P., Kurian, A. W., Pickart, A., Trapane, P., Norton, J. A., Kingham, K., Ford, J. M. 2007; 179 (2): 89-92

  Abstract

  High-penetrance autosomal dominant cancer susceptibility genes such as BRCA2 and MEN1 result in specific patterns of cancers in individuals who inherit germline mutations. Their incidence in the population is relatively low, however, and it is highly unusual to identify individuals with two or more inherited cancer gene mutations. We describe a family with multiple cases of MEN1-associated cancers as well as pancreatic adenocarcinoma, ovarian cancer, and male breast cancer, in which we identified germline mutations in both MEN1 and BRCA2. To our knowledge, this is the first report of a patient with both MEN1 and BRCA2 mutations and with a personal history of hyperparathyroidism and pancreatic neuroendocrine tumors.

  View details for DOI 10.1016/j.cancergencyto.2007.08.009

  View details for Web of Science ID 000251478000001

  View details for PubMedID 18036394

• Asian-Caucasian differences in BRCA1/2 mutation epidemiology Kurian, A., Chun, N., Mills, M., Staton, A., Crawford, B., Ridge, Y., Panabaker, K., Donlon, S., Gong, G., West, D., Ford, J. MARY ANN LIEBERT INC. 2007: 1110–11

  View details for Web of Science ID 000250506100043

• CDH1 truncating mutations in the E-cadherin gene - An indication for total gastrectomy to treat hereditary diffuse gastric cancer ANNALS OF SURGERY Norton, J. A., Ham, C. M., Van Dam, J., Jeffrey, R. B., Longacre, T. A., Huntsman, D. G., Chun, N., Kurian, A. W., Ford, J. M. 2007; 245 (6): 873-879

  Abstract

  Approximately 1% to 3% of all gastric cancers are associated with families exhibiting an autosomal dominant pattern of susceptibility. E-cadherin (CDH1) truncating mutations have been shown to be present in approximately 30% of families with hereditary diffuse gastric cancer (HDGC) and are associated with a significantly increased risk of gastric cancer and lobular breast cancer.Individuals from a large kindred with HDGC who were identified to have a CDH1 mutation prospectively underwent comprehensive screening with stool occult blood testing, standard upper gastrointestinal endoscopy with random gastric biopsies, high-magnification endoscopy with random gastric biopsies, endoscopic ultrasonography, CT, and PET scans to evaluate the stomach for occult cancer. Subsequently, they each underwent total gastrectomy with D-2 node dissection and Roux-en-Y esophagojejunostomy. The stomach and resected lymph nodes were evaluated pathologically.Six patients were identified as CDH1 carriers from a single family. There were 2 men and 4 women. The mean age was 54 years (range, 51-57 years). No patient had any signs or symptoms of gastric cancer. Exhaustive preoperative stomach evaluation was normal in each case, and the stomach and adjacent lymph nodes appeared normal at surgery. However, each patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse gastric adenocarcinoma (pure signet-ring cell type). No patient had lymph node or distant metastases. Each was staged as T1N0M0. Each patient recovered uneventfully without morbidity or mortality.CDH1 mutations in individuals from families with HDGC are associated with gastric cancer in a highly penetrant fashion. CDH1 mutations are an indication for total gastrectomy in these patients. This mutation will identify patients with cancer before other detectable symptoms or signs of the disease.

  View details for DOI 10.1097/01.sla.0000254370.29893.e4

  View details for PubMedID 17522512

• Ductal pattern enhancement on magnetic resonance imaging of the breast due to ductal lavage BREAST JOURNAL Ghanouni, P., Kurian, A. W., Margolis, D., Hartman, A., Mills, M. A., Plevritis, S. K., Ford, J. M., Daniel, B. L. 2007; 13 (3): 281-286

  Abstract

  Our purpose is to describe the appearance of breast ductal enhancement found on magnetic resonance imaging (MRI) after breast ductal lavage (DL). We describe a novel etiology of enhancement in a ductal pattern on postcontrast MRI of the breast. Knowledge of the potential for breast MRI enhancement subsequent to DL, which can mimic the appearance of a pathologic lesion, is critical to the care of patients who undergo breast MRI and DL or other intraductal cannulation procedures.

  View details for PubMedID 17461903

• BRCA1/2 mutations and cancer risk in Asian-Americans American Society of Clinical Oncology Annual Meeting Kurian, A. W., Chun, N. M., Mills, M. A., et al 2007: 10512
• Asian-Caucasian differences in BRCA1/2 mutation epidemiology Building Interdisciplinary Research Careers in Women's Health Annual MeetingA Kurian, A. W., Chun, N. M., Mills, M. A., et al 2007: 1110–11
• A phase II breast cancer chemoprevention study of lovastatin in high-risk women: Initial feasibility data American Society of Clinical Oncology Annual Meeting Kurian, A. W., Sharma, V. B., Schwartz, E. J., et al 2007: 1502
• The role of BRCA1 in DNA repair and chemosensitivity American Society of Clinical Oncology Annual Meeting Sharma, V. B., Kurian, A. W., Feldman, A., Ford, J. M. 2007: 10606
• Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Plevritis, S. K., Kurian, A. W., Sigal, B. M., Daniel, B. L., Ikeda, D. M., Stockdale, F. E., Garber, A. M. 2006; 295 (20): 2374-2384

  Abstract

  Women with inherited BRCA1/2 mutations are at high risk for breast cancer, which mammography often misses. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans.To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone.A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. The accuracy of mammography and breast MRI was estimated from published data in high-risk women. Breast cancer survival in the absence of screening was based on the Surveillance, Epidemiology and End Results database of breast cancer patients diagnosed in the prescreening period (1975-1981), adjusted for the current use of adjuvant therapy. Utilization rates and costs of diagnostic and treatment interventions were based on a combination of published literature and Medicare payments for 2005.The survival benefit, incremental costs, and cost-effectiveness of MRI screening strategies, which varied by ages of starting and stopping MRI screening, were computed separately for BRCA1 and BRCA2 mutation carriers.Screening strategies that incorporate annual MRI as well as annual mammography have a cost per quality-adjusted life-year (QALY) gained ranging from less than 45,000 dollars to more than 700,000 dollars, depending on the ages selected for MRI screening and the specific BRCA mutation. Relative to screening with mammography alone, the cost per QALY gained by adding MRI from ages 35 to 54 years is 55,420 dollars for BRCA1 mutation carriers, 130,695 dollars for BRCA2 mutation carriers, and 98,454 dollars for BRCA2 mutation carriers who have mammographically dense breasts.Breast MRI screening is more cost-effective for BRCA1 than BRCA2 mutation carriers. The cost-effectiveness of adding MRI to mammography varies greatly by age.

  View details for PubMedID 16720823

• Biomedical terahertz imaging with a quantum cascade laser APPLIED PHYSICS LETTERS Kim, S. M., Hatami, F., Harris, J. S., Kurian, A. W., Ford, J., King, D., Scalari, G., Giovannini, M., Hoyler, N., Faist, J., Harris, G. 2006; 88 (15)

  View details for DOI 10.1063/1.2194229

  View details for Web of Science ID 000236796400112

• Comparative Analysis of Bio-Medical Imaging at 3.7 Terahertz with a High Power Quantum Cascade Laser LEOS 2006-19th Annual Meeting of the IEEE Lasers and Electro-Optics Society Kim, S. M., Hatami, F., Gu, A., Kurian, A. W., et al 2006: 231
• A clinic-based study of BRCA1/2 mutation epidemiology in Asians San Antonio Breast Cancer Symposium Kurian, A. W., Chun, N. M., Millls, M. A., et al 2006
• Opinions of women with high inherited breast cancer risk about prophylactic mastectomy: an initial evaluation from a screening trial including magnetic resonance imaging and ductal lavage HEALTH EXPECTATIONS Kurian, A. W., Hartman, A. R., Mills, M. A., Ford, J. M., Daniel, B. L., Plevritis, S. K. 2005; 8 (3): 221-233

  Abstract

  Prophylactic mastectomy (PM) is often considered, but variably chosen by women at high inherited risk of breast cancer; few data exist on patient tolerance of intensive breast screening as an alternative to PM. We performed an evaluation of high-risk women's tolerance of a breast screening protocol using clinical breast examination, mammography, breast magnetic resonance imaging (MRI) and ductal lavage (DL), and of change in attitudes toward PM after screening.A questionnaire assessing tolerance of screening procedures and change in opinion towards PM was designed and administered to 43 study participants, after a median follow-up of 13 months. Responses were evaluated according to patient characteristics, including type of study-prompted interventions, BRCA mutation status, and prior history of cancer, via univariate analysis.Most patients [85.3% (68.9-95.1%)] were more opposed or unchanged in their attitudes towards PM after study participation, with only 14.7% (5.0-31.1%) less opposed (P = 0.017) despite a short-interval follow-up MRI rate of 71.7% and a biopsy rate of 37%. Lower rates of maximal discomfort were reported with mammogram [2.8% (0-14.5%)] and MRI [5.6% (0-18.7%)] than with DL [28.6% (14.6-46.3%)], with P = 0.035.Most high-risk women tolerated intensive breast screening well; they were not more inclined towards PM after participating. Future studies should prospectively evaluate larger numbers of high-risk women via multivariate analysis, to determine characteristics associated with preference for breast screening vs. PM.

  View details for PubMedID 16098152

• Ductal lavage of fluid-yielding and non-fluid-yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high inherited breast cancer risk CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kurian, A. W., Mills, M. A., Jaffee, M., Sigal, B. M., Chun, N. M., Kingham, K. E., Collins, L. C., Nowels, K. W., Plevritis, S. K., Garber, J. E., Ford, J. M., Hartman, A. R. 2005; 14 (5): 1082-1089

  Abstract

  Nipple fluid production and atypical breast duct cells in women at high risk of breast cancer have been associated with further increased risk. Most publications on ductal lavage for cell collection report cannulating fluid-yielding ducts only. We report lavage of fluid-yielding and non-fluid-yielding ducts in women at high inherited breast cancer risk.A pilot breast cancer screening study including ductal lavage was conducted in 75 women at high inherited risk, 56 (74.7%) of whom had BRCA1/2 mutations. Ductal lavage was attempted in any duct identifiable with a catheter.Ducts were successfully catheterized in 60 of 75 patients (80%). Successfully catheterized patients were younger (median age 41 versus 53 years, P = 0.0003) and more often premenopausal (51.7% versus 20%, P = 0.041). Thirty-one successfully catheterized patients [51.6%, 95% confidence interval (39.4-63.9%)] had non-fluid-yielding ducts only. Seventeen patients [28.3% (18.5-40.9%)] had atypical cells. Twelve of seventeen [70.6% (46.8-87.2%)] samples with atypia were from non-fluid-yielding ducts. Patients with non-fluid-yielding ducts (versus fluid-yielding ducts) were more likely to have had prior cancer (48.4% versus 17.2%, P = 0.014) or chemotherapy (45.2% versus 17.2%, P = 0.027); this was also true in patients with atypia from non-fluid-yielding ducts.Successfully lavaged women were younger and more often premenopausal. Atypical cells can be found in non-fluid-yielding ducts in patients at high inherited breast cancer risk. Non-fluid-yielding ducts, and atypia from non-fluid-yielding ducts, are more common in patients with prior cancer and chemotherapy. Larger studies are needed to identify risk factors and prognostic significance associated with atypia and non-fluid-yielding ducts in high-risk populations, and define their role as biomarkers.

  View details for PubMedID 15894656

• Histologic types of epithelial ovarian cancer: have they different risk factors? GYNECOLOGIC ONCOLOGY Kurian, A. W., Balise, R. R., McGuire, V., Whittemore, A. S. 2005; 96 (2): 520-530

  Abstract

  The histologic types of epithelial ovarian cancer differ in clinical behavior, descriptive epidemiology, and genetic origins. The goals of the current study were to characterize further the relation of histologic-specific ovarian cancer risks to reproductive and lifestyle attributes.The authors conducted a pooled analysis of 10 case-control studies of ovarian cancer in US White women, involving 1834 patients with invasive epithelial ovarian cancer (1067 serous, 254 mucinous, 373 endometrioid, and 140 clear cell) and 7484 control women.Risks of all four histological types were inversely associated with parity and oral contraceptive use, but the histologic types showed different associations with nonreproductive factors. Unique associations include an inverse relation of serous cancer risk to body mass index, a positive relation of mucinous cancer risk to cigarette smoking, and a weakly positive relation of endometrioid cancer risk to body mass index. Risk of all histologic types was unassociated with age at menarche, age at menopause, a history of infertility, noncontraceptive estrogen use, and alcohol consumption.The most important modifiers of ovarian cancer risk (parity and oral contraceptive use) showed similar associations across the histologies. Nevertheless, the unique associations seen for other modifiers support the conjecture that the histologic types of epithelial ovarian cancer have different etiologies, which should be addressed in future investigations of the molecular basis of ovarian cancers and their responses to therapies.

  View details for DOI 10.1016/j.gygno.2004.10.037

  View details for Web of Science ID 000226636600041

  View details for PubMedID 15661246

• Predicting US breast cancer mortality rate in the year 2010 American Association for Cancer Research Annual Meeting Plevritis, S. K., Sigal, B. M., Kurian, A. W., et al 2005
• Estimating the life years gained from breast MRI screening in women with BRCA1/2 mutations The 27th Annual Meeting of the Society for Medical Decision Making Plevritis, S. K., Sigal, B. M., Kurian, A. W. 2005
• Breast cancer risk management choices by women with inherited breast cancer predisposition: a preliminary analysis San Antonio Breast Cancer Symposium Kurian, A. W., Hartman, A., Mills, M. A., et al 2005
• Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma CANCER Hartman, A. R., Daniel, B. L., Kurian, A. W., Mills, M. A., Nowels, K. W., Dirbas, F. M., Kingham, K. E., Chun, N. M., Herfkens, R. J., Ford, J. M., Plevritis, S. K. 2004; 100 (3): 479-489

  Abstract

  Intensive screening is an alternative to prophylactic mastectomy in women at high risk for developing breast carcinoma. The current article reports preliminary results from a screening protocol using high-quality magnetic resonance imaging (MRI), ductal lavage (DL), clinical breast examination, and mammography to identify early malignancy and high-risk lesions in women at increased genetic risk of breast carcinoma.Women with inherited BRCA1 or BRCA2 mutations or women with a >10% risk of developing breast carcinoma at 10 years, as estimated by the Claus model, were eligible. Patients were accrued from September 2001 to May 2003. Enrolled patients underwent biannual clinical breast examinations and annual mammography, breast MRI, and DL.Forty-one women underwent an initial screen. Fifteen of 41 enrolled women (36.6%) either had undergone previous bilateral oophorectomy and/or were on tamoxifen at the time of the initial screen. One patient who was a BRCA1 carrier had high-grade ductal carcinoma in situ (DCIS) that was screen detected by MRI but that was missed on mammography. High-risk lesions that were screen detected by MRI in three women included radial scars and atypical lobular hyperplasia. DL detected seven women with cellular atypia, including one woman who had a normal MRI and mammogram.Breast MRI identified high-grade DCIS and high-risk lesions that were missed by mammography. DL detected cytologic atypia in a high-risk cohort. A larger screening trial is needed to determine which subgroups of high-risk women will benefit and whether the identification of malignant and high-risk lesions at an early stage will impact breast carcinoma incidence and mortality.

  View details for DOI 10.1002/cncr.11926

  View details for PubMedID 14745863

• Ductal lavage of non-fluid yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high genetic risk for breast cancer American Society of Clinical Oncology Annual Meeting Kurian, A. W., Mills, M. A., Nowels, K. W., et al 2004: 9535
• Identification of ductal atypia with MR galactography American Society of Clinical Oncology Annual Meeting Hartman, A., Mills, M. A., Kurian, A. W., Ford, J. M., Smith, D. N., Daniel, B. L. 2004: 1035
• Magnetic resonance galactography: a new technique for localization of ductal atypia. San Antonio Breast Cancer Symposium Hartman, A., Kurian, A. W., Mills, M. A., et al 2004: S190
• A pilot breast cancer screening trial for women at high inherited risk using clinical breast exam, mammography, breast magnetic resonance imaging, and ductal lavage: updated results after median follow-up of fourteen months San Antonio Breast Cancer Symposium Kurian, A. W., Daniel, B. L., Mills, M. A., et al 2004
• Results from a pilot breast cancer screening trial using a combination of clincal breast exam, mammography, breast MRI, and ductal lavage in a high-risk population San Antonio Breast Cancer Symposium Hartman, A., Kurian, A. W., Mills, M. A., et al 2003