Bio

Bio


Allison W. Kurian, M.D., M.Sc. is an Assistant Professor of Medicine and of Health Research and Policy at Stanford University School of Medicine. She received her medical degree from Harvard Medical School, trained as a resident in Internal Medicine at the Massachusetts General Hospital, and completed her fellowship training in Medical Oncology along with a master’s degree in Epidemiology at Stanford University. As Associate Director of the Stanford Program in Clinical Cancer Genetics, and physician leader of the Stanford Women’s Cancer Genetics Clinic, her clinical practice centers on women at high risk for developing breast and gynecologic cancers. Dr. Kurian’s research focuses on the identification of women with elevated breast and gynecologic cancer risk, and on the development and evaluation of novel techniques for early cancer detection and risk reduction. Her research has been supported by the National Institutes of Health, the Komen Foundation, the American Society of Clinical Oncology, the California Breast Cancer Research Program, the Cancer Research and Prevention Foundation, the Robert Wood Johnson Foundation, and the Breast Cancer Research Foundation.

Clinical Focus


  • Breast Cancer Risk
  • Cancer > Breast Cancer
  • Medical Oncology
  • Cancer Genetics

Academic Appointments


Administrative Appointments


  • Oncology Consultant, Breast Cancer Working Group, Cancer Intervention and Surveillance Modeling Network (CISNET) (2014 - Present)
  • Associate Member, Canary Center at Stanford for Cancer Early Detection (2014 - Present)
  • Track Leader, Cancer Prevention and Epidemiology, Scientific Program Committee, American Society of Clinical Oncology (2013 - 2014)
  • Director, Cancer Education Seminar, Stanford Division of Oncology (2013 - Present)
  • Panel on Clinical Guidelines Development for Breast Cancer Risk Reduction, National Comprehensive Cancer Network (2013 - Present)
  • Advisory Committee, California HealthCare Foundation (2012 - Present)
  • Scientific Program Committee, Cancer Prevention and Epidemiology, American Society of Clinical Oncology (2011 - 2014)
  • Scientific Program Committee, Quality Care Symposium, American Society of Clinical Oncology (2012 - 2015)
  • Scientific Program Committee, Genetic and Molecular Epidemiology, American Association for Cancer Research (2011 - 2012)
  • Board of Directors, Santa Clara County, American Cancer Society (2011 - Present)
  • Panel on Clinical Guidelines Development for Genetic/ Familial Risk: Breast and Ovarian Cancer, National Comprehensive Cancer Network (2009 - Present)
  • Program Committee, Professional Development, American Society of Clinical Oncology (2008 - 2011)
  • Career Development Subcommittee, American Society of Clinical Oncology (2008 - 2011)
  • Associate Director, Stanford Clinical Cancer Genetics Program (2007 - Present)

Honors & Awards


  • Suzanne Pride Bryan Award for Breast Cancer Research, Stanford University Cancer Institute (2013)
  • Top 12 publications funded by the Epidemiology and Genomics Research Program, National Cancer Institute (2011)
  • New Clinical Investigator Award, Stanford University Cancer Institute (2011)
  • Translational Research Award, California Breast Cancer Research Program (2010)
  • Jan Weimer Faculty Chair for Breast Oncology, Stanford University Cancer Institute (2008)
  • Physician Faculty Scholars Award, Robert Wood Johnson Foundation (2008)
  • Cornelius L. Hopper Research Abstract Award, California Breast Cancer Research Program (2007)
  • BIRCWH K12 Scholar Award, National Institutes of Health (2006)
  • Young Investigator Award, American Society of Clinical Oncology (2005)
  • Fellowship Award, Cancer Research and Prevention Foundation (2005)
  • Fellowship Award, California Breast Cancer Research Program (2005)
  • Merit Award, American Society of Clinical Oncology (2004)

Professional Education


  • Internship:Massachusetts General Hospital (2000) MA
  • Residency:Massachusetts General Hospital (2002) MA
  • Medical Education:Harvard Medical School (1999) MA
  • M.Sc., Stanford University, Epidemiology (2006)
  • Board Certification: Medical Oncology, American Board of Internal Medicine (2005)
  • Fellowship:Stanford University School of Medicine (2005) CA
  • B.A., Honors, Stanford University, Human Biology (1995)

Community and International Work


  • FORCE: Facing Our Risk of Cancer Empowered

    Topic

    Scientific Advisory Board

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • American Cancer Society, Santa Clara County

    Topic

    Board Member

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Breast Cancer Connections, Palo Alto, CA

    Topic

    Patient and community education

    Populations Served

    All

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


I aim to improve the outcomes of women's cancers through clinically-oriented research on genetic risk assessment, risk-adapted screening and prevention. My research employs methods from the population sciences, in close collaboration with the Stanford Division of Epidemiology, Department of Radiology and Center for Biomedical Informatics Research; the Cancer Prevention Institute of California; and the Palo Alto Medical Foundation Research Institute.

I have led epidemiologic studies of risk factors for breast and ovarian cancer, clinical trials of novel approaches to the prevention of breast cancer, and decision analyses of strategies to optimize breast and ovarian cancer outcomes. I currently lead the Oncoshare project at Stanford, a multi-institutional breast cancer outcomes research database that integrates information from electronic medical records and the population-based California Cancer Registry. Other recent work includes the development of a clinical decision support tool to help women with BRCA1/2 mutations reduce their cancer risks (http://brcatool.stanford.edu).

Clinical Trials


  • A Phase 3, Multi-Center Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer Not Recruiting

    The goal of this study was to determine the effect on overall survival and progression free survival by adding iniparib (BSI-201/SAR240550) to the combination of gemcitabine/carboplatin in adult patients with triple negative breast cancer (estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative). Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the poly (ADP-ribose) polymerase (PARP) inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Charlene Kranz, (650) 498 - 7977.

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  • Neratinib in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer Recruiting

    This phase II study will test cancer to see if it has a HER2 mutation and, if so, see how HER2 mutated cancer responds to treatment with neratinib.

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  • Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer Not Recruiting

    RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating patients with hormone receptor-positive breast cancer. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating postmenopausal women who have received hormone therapy for hormone receptor-positive breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer Not Recruiting

    This randomized phase III trial studies doxorubicin, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with lymph node-positive or high-risk, lymph node-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether doxorubicin, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab in treating breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pei-Jen Chang, (650) 725 - 0866.

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  • A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Breast Cancer After Adjuvant Therapy Not Recruiting

    The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with HER-2-positive breast cancer. The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With LCL161 in Patients With Triple Negative Breast Cancer Recruiting

    To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer whose tumors are positive for a defined pattern of gene expression

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  • A Trial Using Novel Markers to Predict Malignancy in Elevated-Risk Women Recruiting

    The Novel Markers Trial will compare the safety, feasibility and effectiveness of two different epithelial ovarian cancer screening strategies that use CA125 and add HE4 as either a first or second line screen. This study is the next step in a larger research effort to develop a blood test that can be used as a screening method for the early detection of epithelial ovarian cancer.

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  • A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer Not Recruiting

    This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combination with paclitaxel (and pertuzumab, if applicable) in patients with HER2-positive, locally advanced or metastatic breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Annabel Castaneda, 650-498-7977.

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  • A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZDO530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer Recruiting

    The investigators propose to conduct a Phase I/randomized Phase II study design in order to test the tolerability and efficacy or AZD0530 when used together with anastrozole in therapy of ER+ and/or PR+ postmenopausal breast cancer. The Phase I pharmacokinetic (PK) cohort of the study (cohort A) will be conducted in postmenopausal women with metastatic disease and will ascertain safety and toxicity. Patients in the randomized Phase II cohort of the study (cohort B) will consist of postmenopausal women with locally advanced ER+ breast cancer who are randomized to either neoadjuvant treatment with anastrozole plus placebo, or anastrozole in combination with AZD0530. The Phase II cohort will permit extended assays of tolerability, initial estimates of efficacy, and the investigation of molecular (protein and RNA expression profiles) and cellular assays (measures of TICs) as predictors of drug efficacy.

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  • A Study of Pertuzumab in Combination With Herceptin (Trastuzumab) And Vinorelbine in First Line in Patients With Metastatic or Locally Advanced HER2-Positive Breast Cancer Not Recruiting

    This two-cohort, open-label, multicenter, phase II study will assess the safety and efficacy of pertuzumab given in combination with Herceptin (trastuzumab) and vinorelbine in first line in patients with metastatic or locally advanced HER2-positive breast cancer. Patients will receive pertuzumab 840 mg and Herceptin 8 mg/kg administered sequentially as separate iv infusions on Days 1 and 2, respectively, of Cycle 1. From Cycle 2 onwards, patients will receive pertuzumab 420 mg and Herceptin 6 mg/kg, administered either sequentially as separate iv infusions on Day 1 and Day 1 or 2, respectively (Cohort 1) or together in one infusion bag on Day 1 (Cohort 2) every 3 weeks. Vinorelbine will be administered at 25 mg/m2 iv on Days 2 and 9 of Cycle 1, and at 30-35 mg/m2 on Days 1 and 8 (or Days 2 and 9) of each following 3-week cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs, or withdrawal of consent or death! .

    Stanford is currently not accepting patients for this trial. For more information, please contact Naheed Mangi, 650-723-0658.

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  • The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer Recruiting

    The Study Evaluating Efficacy And Tolerability of Veliparib in Combination with Temozolomide or Veliparib/Placebo in Combination with Carboplatin and Paclitaxel in Subjects with locally recurrent Breast Cancer not amenable to therapy with curative intent, or metastatic breast cancer and a documented (BRCA1) and (BRCA2) deleterious germline mutation.

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  • Phase II Trial - Breast Cancer Chemoprevention by Lovastatin Not Recruiting

    The purpose of the study is to determine whether oral lovastatin, used for 6 months, results in a decrease of abnormal breast duct cytology in women at high inherited breast cancer risk.

    Stanford is currently not accepting patients for this trial. For more information, please contact Meredith Mills, (650) 724 - 5223.

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  • Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole Not Recruiting

    There are no treatments specifically approved after recurrence or progression on a NSAI. In light of the need for new treatment options for postmenopausal women after failure of prior non steroidal aromatase inhibitors (NSAI) therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer Recruiting

    This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected.

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  • Genetic & Pathological Studies of BRCA1/BRCA2: Associated Tumors & Blood Samples Recruiting

    1. To establish a demographic database to evaluate the efficacy of medical interventions in patients and relatives who carry BRCA1 and 2 mutations and to compare these outcomes to patients who do not carry a BRCA1 or 2 mutation. 2. To obtain blood samples from patients who undergo genetic testing to a) evaluate the incidence of genetic modifier polymorphisms involved in the development of cancer in BRCA1 and 2 mutation carriers and to compare this incidence to non-BRCA 1 and 2 carriers. b) to understand the interaction of genetic modifiers and BRCA1 and 2 in the development of cancer. c) to determine the effect of environmental influences on the incidence of polymorphisms in genetic modifiers and on the penetrance of BRCA1 and 2 mutations by linking information from our demographic database to blood samples and 3. To obtain tumor tissue from BRCA1 and 2 carriers to utilize for gene expression studies. 4. To establish a cohort of sporadic breast cancer patients, or women with no family history of cancer in a first degree relative, to serve as a comparison group to women with strong family history of breast cancer. 5. To establish a cohort of healthy volunteers without personal or family history of cancer to serve as a comparison group to women with sporadic and familial breast cancer.

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  • Factors Influencing Decision-Making About the Use of Chemoprevention in Women at Increased Risk for Breast Cancer Not Recruiting

    RATIONALE: Learning about how patients make decisions about using chemoprevention may help doctors plan treatment in which more patients are willing to choose chemoprevention to reduce their breast cancer risk. PURPOSE: This clinical trial studies factors influencing decision-making about the use of chemoprevention in women at increased risk for breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • 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

  • Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment. Journal of clinical oncology : official journal of the American Society 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

    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 PubMedID 24733792

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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): 4752-4758

    Abstract

    There are established differences in breast cancer epidemiology between Asian and white individuals, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian individuals are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian individuals. We compared the performance in Asian and white individuals of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II.We evaluated BRCAPRO and Myriad II in 200 Asian individuals and a matched control group of 200 white individuals who were tested for BRCA1/2 mutations at four cancer genetics clinics, by comparing numbers of observed versus predicted mutation carriers and by evaluating area under the receiver operating characteristic curve (AUC) for each model.BRCAPRO and Myriad II accurately predicted the number of white BRCA1/2 mutation carriers (25 observed v 24 predicted by BRCAPRO; 25 predicted by Myriad II, P > or = .69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P < or = 3 x 10(-7)). For BRCAPRO, this racial difference reflects substantial underprediction of Asian BRCA2 mutation carriers (26 observed v 4 predicted; P = 1 x 10(-30)); for Myriad II, separate mutation predictions were not available. For both models, AUCs were nonsignificantly lower in Asian than white individuals, suggesting less accurate discrimination between Asian carriers and noncarriers.Both BRCAPRO and Myriad II underestimated the proportion of BRCA1/2 mutation carriers, and discriminated carriers from noncarriers less well, in Asian compared with white individuals.

    View details for DOI 10.1200/JCO.2008.16.8310

    View details for Web of Science ID 000259902800011

    View details for PubMedID 18779604

  • 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

  • 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

  • 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 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

  • 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

    View details for DOI 10.1148/radiol.13131217

  • 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
  • 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
  • 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

  • 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

  • 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

  • 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

  • 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
  • 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

  • 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

  • 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 BRCRAPRO 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

  • 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

  • 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

  • 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

  • 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

  • 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

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