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

All Publications

• Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for 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., West, R. B., Horst, K., Gomez, S. L., Ford, J. M., Sledge, G. W., Kurian, A. W. 2018

  Abstract

  Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC.Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM and OM. For a subgroup with TILs data available, we explored the relationship between TILs and peripheral lymphocyte counts.1,463 Stage I-III TNBC patients were diagnosed from 2000-2014; 1113 (76%) received neoadjuvant/adjuvant chemotherapy within one year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.16-0.35) and BCM (HR: 0.19, CI: 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (N=70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.

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

  View details for PubMedID 29581131

• 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

  Abstract

  Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice.To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer.For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 (BRCA1/2) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories.Type of testing (multiple-gene sequencing vs BRCA1/2-only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines.Among 5026 patients (mean [SD] age, 59.9 [10.7]), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2-only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2-only testing, 74.4%;in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2-only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2-only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2-only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2-only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2-only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 (BRCA1/2, 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%).Multiple-gene sequencing rapidly replaced BRCA1/2-only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.

  View details for DOI 10.1001/jamaoncol.2018.0644

  View details for PubMedID 29801090

• 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

  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., Katz, S. J., Jagsi, R. 2017; 317 (5): 531–34

  View details for DOI 10.1001/jama.2016.16918

  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., Jagsi, R., 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 DOI 10.1093/jnci/djx239

  View details for PubMedID 29237009

• Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women Journal of Clinical Oncology Precision Oncology Kurian, A. W., Hughes, E., Handorf, E. A., Gutin, A., Allen, B., Hartman, A., Hall, M. J. 2017; online publication ahead of print, June 27

  View details for DOI 10.1200/PO.16.00066

• 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 Web of Science ID 000302622900014

  View details for PubMedID 22231042

  View details for PubMedCentralID PMC3295552

• 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. ; 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

• Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012. JAMA Plevritis, S. K., Munoz, D., Kurian, A. W., Stout, N. K., Alagoz, O., Near, A. M., Lee, S. J., van den Broek, J. J., Huang, X., Schechter, C. B., Sprague, B. L., Song, J., de Koning, H. J., Trentham-Dietz, A., van Ravesteyn, N. T., Gangnon, R., Chandler, Y., Li, Y., Xu, C., Ergun, M. A., Huang, H., 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 DOI 10.1001/jama.2017.19130

  View details for PubMedID 29318276

• 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: 172462

  Abstract

  Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features. A network strategy was used to integrate all image features and classify patients into different risk groups. The prognostic value of imaging-based stratification was evaluated in relation to clinical-pathologic factors with multivariable Cox regression. Results Three intratumoral subregions with high, intermediate, and low MR perfusion were identified and showed high consistency between the two cohorts. Patients in both cohorts were stratified according to network analysis of multiregional image features regarding RFS (log-rank test, P = .002 for both). Aggressive tumors were associated with a larger volume of the poorly perfused subregion as well as interaction between poorly and moderately perfused subregions and surrounding parenchyma. At multivariable analysis, the proposed MSI-based marker was independently associated with RFS (hazard ratio: 3.42; 95% confidence interval: 1.55, 7.57; P = .002) adjusting for age, estrogen receptor (ER) status, progesterone receptor status, human epidermal growth factor receptor type 2 (HER2) status, tumor volume, and pathologic complete response (pCR). Furthermore, imaging helped stratify patients for RFS within the ER-positive and HER2-positive subgroups (log-rank test, P = .007 and .004) and among patients without pCR after neoadjuvant chemotherapy (log-rank test, P = .003). Conclusion Breast cancer consists of multiple spatially distinct subregions. Imaging heterogeneity is an independent prognostic factor beyond traditional risk predictors.

  View details for DOI 10.1148/radiol.2018172462

  View details for PubMedID 29714680

• 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., Sprague, B. L., Trentham-Dietz, A., Gangnon, R., Kurian, A. W., Weedon-Fekjaer, H., 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 DOI 10.1177/0272989X17700624

  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., Ho, J. C., Shin, V. Y., Kurian, A. W., Tai, E., Esserman, L. J., Weitzel, J. N., Lin, P. H., Field, M., Domchek, S. M., Lo, J., 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 DOI 10.18632/oncotarget.23471

  View details for PubMedID 29487695

  View details for PubMedCentralID PMC5814262

• Patient communication of cancer genetic test results in a diverse population. Translational behavioral medicine Ricker, C. N., Koff, R. B., Qu, C., Culver, J., Sturgeon, D., Kingham, K. E., Lowstuter, K., Chun, N. M., Rowe-Teeter, C., Lebensohn, A., Levonian, P., Partynski, K., Lara-Otero, K., Hong, C., Petrovchich, I. M., Mills, M. A., Hartman, A. R., Allen, B., Ladabaum, U., McDonnell, K., 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 DOI 10.1093/tbm/ibx010

  View details for PubMedID 29385580

• 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., Jagsi, R., 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 DOI 10.1200/JCO.2017.76.2369

  View details for PubMedID 29528794

• Measuring serum melatonin in postmenopausal women: Implications for epidemiologic studies and breast cancer studies. PloS one Chu, L. W., John, E. M., Yang, B., Kurian, A. W., Zia, Y., Yu, K., 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 DOI 10.1371/journal.pone.0195666

  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., Cronin, K. A., Kurian, A. W., Andridge, R. 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 DOI 10.1158/1055-9965.EPI-17-0627

  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., Li, Y., Kurian, A. W., Sabolch, A., Hamilton, A. S., Ward, K. C., Katz, S. J., Hawley, S. T., Jagsi, R. 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 DOI 10.1016/j.ijrobp.2018.01.020

  View details for PubMedID 29439886

• 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

• 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)

  View details for DOI 10.1001/jamasurg.2016.4749

  View details for Web of Science ID 000398101400016

• 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

• 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

• Treatment decisions and employment of breast cancer patients: Results of a population-based survey. Cancer Jagsi, R., Abrahamse, P. H., Lee, K. L., Wallner, L. P., Janz, N. K., Hamilton, A. S., Ward, K. C., Morrow, M., 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 DOI 10.1002/cncr.30959

  View details for PubMedID 28990155

• 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

  View details for DOI 10.1002/cncr.30324

  View details for Web of Science ID 000394719100007

• 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 DOI 10.1093/ajcp/aqx063

  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., Wallner, L. P., Kurian, A. W., Katz, S. J., Abrahamse, P., 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 DOI 10.1177/0272989X17724441

  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., Hall, E., Petrovchich, I. M., Mills, M. A., Kingham, K. E., Koff, R., Chun, N. M., Levonian, P., 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 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., Jagsi, R., 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 DOI 10.1007/s10549-017-4377-3

  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., Li, B., Sun, X., Cao, G., Rubin, D. L., Napel, S., Ikeda, D. M., Kurian, A. W., Li, R. 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 DOI 10.1148/radiol.2017162823

  View details for PubMedID 28708462

• Trends in Reoperation After Initial Lumpectomy for Breast Cancer: Addressing Overtreatment in Surgical Management. JAMA oncology Morrow, M., Abrahamse, P., Hofer, T. P., Ward, K. C., Hamilton, A. S., Kurian, A. W., Katz, S. J., Jagsi, R. 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 DOI 10.1001/jamaoncol.2017.0774

  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

  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

• 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 Web of Science ID 000380072700008

  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 Web of Science ID 000378880400020

  View details for PubMedID 27280630

• 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

• 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 Web of Science ID 000377391900002

  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

• 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

  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

  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 Web of Science ID 000366970600002

  View details for PubMedID 26187060

• 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., Kurian, A. W., Wakelee, H., Wang, A., Paskett, E., Han, J., 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 DOI 10.1111/bjd.14766

  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 Web of Science ID 000363978000024

  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

  View details for DOI 10.1001/jamaoncol.2015.2690

  View details for Web of Science ID 000383675900013

• 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 Web of Science ID 000360777700009

  View details for PubMedID 26207792

• 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

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

  View details for Web of Science ID 000359348400001

  View details for PubMedID 26265211

• 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 Web of Science ID 000359320500019

  View details for PubMedID 26063477

• 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

  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

• 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

• 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

• Linking electronic health records to better understand breast cancer patient pathways within and between two health systems eGEMs (Generating Evidence & Methods to improve patient outcomes) Thompson, C. A., Kurian, A. W., Luft, H. S. 2015; 3 (1)

  View details for DOI 10.13063/2327-9214.1127

• 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

• 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

• 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

• 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

• 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

• Response. 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., Ojeda-Fournier, H., Kurian, A. W., Love, E., Ryan, L., Ikeda, D. M. 2014; 271 (3): 927-928

  View details for DOI 10.1148/radiol.14144013

  View details for PubMedID 24848959

• 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

• 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

  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

• 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

• 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

• 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 Web of Science ID 000314408700008

  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
• 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

• 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 Web of Science ID 000311025000016

  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 Web of Science ID 000306210100009

  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

• 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 Web of Science ID 000305335000005

  View details for PubMedID 22586443

  View details for PubMedCentralID PMC3346739

• 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

• 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

• In reply to "Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: More Trouble With Phenocopies" by Evans et al JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Whittemore, A. S. 2012; 30: 1143-1144
• Genetic Polymorphisms as Predictors of Breast Cancer Risk CURRENT BREAST CANCER REPORTS de Bruin, M. A., Ford, J. M., Kurian, A. W. 2012: DOI 10.1007/s12609-0
• 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

• 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

• 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 Web of Science ID 000298136500016

  View details for PubMedID 22042950

  View details for PubMedCentralID PMC3236651

• 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 Web of Science ID 000294346700027

  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 Web of Science ID 000290227900017

  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
• 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

• 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 Web of Science ID 000273418000010

  View details for PubMedID 19996031

  View details for PubMedCentralID PMC2815712

• 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

• 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

• 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 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 Web of Science ID 000265125000009

  View details for PubMedID 19336551

• In reply to 'Tailoring BRCAPRO to Asian Americans?' by S. Chen et al JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Whittemore, A. S., Ford, J. M. 2009; 27: 643-4
• 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 Web of Science ID 000256823500010

  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

• 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 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

• 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 Web of Science ID 000246873000007

  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 Web of Science ID 000245992200010

  View details for PubMedID 17461903

• 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

• 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 Web of Science ID 000237734400023

  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

• 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 Web of Science ID 000231345500004

  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 Web of Science ID 000229032000008

  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

• 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 Web of Science ID 000188611400006

  View details for PubMedID 14745863