A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at Risk of Hereditary Breast Cancer.

BACKGROUND The National Comprehensive Cancer Network recommends that women who carry gene variants that confer substantial risk for breast cancer consider risk-reduction strategies, that is, enhanced surveillance (breast magnetic resonance imaging and mammography) or prophylactic surgery. Pathogenic variants can be detected in women with a family history of breast or ovarian cancer syndromes by multigene panel testing. OBJECTIVES To investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy. METHODS We estimated effectiveness and lifetime costs from a payer perspective for two strategies in two hypothetical cohorts of women (40-year-old and 50-year-old cohorts) who meet the National Comprehensive Cancer Network-defined family history criteria for multigene testing. The two strategies were the usual test strategy for variants in BRCA1 and BRCA2 and the seven-gene test strategy for variants in BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, and PALB2. Women found to have a pathogenic variant were assumed to undergo either prophylactic surgery or enhanced surveillance. RESULTS The incremental cost-effectiveness ratio for the seven-gene test strategy compared with the BRCA1/2 test strategy was $42,067 per life-year gained or $69,920 per quality-adjusted life-year gained for the 50-year-old cohort and $23,734 per life-year gained or $48,328 per quality-adjusted life-year gained for the 40-year-old cohort. In probabilistic sensitivity analysis, the seven-gene test strategy cost less than $100,000 per life-year gained in 95.7% of the trials for the 50-year-old cohort. CONCLUSIONS Testing seven breast cancer-associated genes, followed by risk-reduction management, could cost-effectively improve life expectancy for women at risk of hereditary breast cancer.

[1]  B. Karlan,et al.  Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers. , 2013, American journal of obstetrics and gynecology.

[2]  Tina Pesaran,et al.  Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients , 2014, Genetics in Medicine.

[3]  Yuya Kobayashi,et al.  Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment. , 2015, JAMA oncology.

[4]  S. Narod,et al.  Genetic risk assessment and prevention: the role of genetic testing panels in breast cancer , 2015, Expert review of anticancer therapy.

[5]  Anne Wallace,et al.  Breast Cancer Risk Reduction, Version 2.2015. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[6]  Dana M. Goos-Root,et al.  Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory , 2015, PloS one.

[7]  E. Arias United States Life Tables, 2011. , 2015, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[8]  Frederic M. Waldman,et al.  Cost Effectiveness of Sequencing 34 Cancer-Associated Genes as an Aid for Treatment Selection in Patients with Metastatic Melanoma , 2015, Molecular Diagnosis & Therapy.

[9]  J. Klijn,et al.  Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. , 2001, The New England journal of medicine.

[10]  G. Fonarow,et al.  ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. , 2014, Circulation.

[11]  Vijai Joseph,et al.  Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  K. Noyes,et al.  Cost Effectiveness Analysis of Genetic Testing for Breast and Ovarian Cancer Susceptibility Genes: BRCA1 and BRCA2 , 2014, The breast journal.

[13]  J. Hopper,et al.  Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. , 2003, American journal of human genetics.

[14]  Lester R Curtin,et al.  U.S. decennial life tables for 1999-2001, United States life tables. , 2008, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[15]  Kenneth Offit,et al.  Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention , 2014, Science.

[16]  C. Boland,et al.  Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population , 2010, Cancer Prevention Research.

[17]  A. Jakubowska,et al.  Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis. , 2015, The Lancet. Oncology.

[18]  J. Brazier,et al.  Health-state utility values in breast cancer , 2010, Expert review of pharmacoeconomics & outcomes research.

[19]  J. Wardle,et al.  Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based Testing , 2014, Journal of the National Cancer Institute.

[20]  L. Korde,et al.  Genetics of breast cancer: a topic in evolution. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  E. Feuer,et al.  Cancer survival among adults: US SEER Program, 1988-2001: patient and tumor characteristics. , 2007 .

[22]  L. J. Schelven,et al.  Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group , 2004 .

[23]  K M Kuntz,et al.  Decision analysis--effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. , 1997, The New England journal of medicine.

[24]  S. Cummings,et al.  Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness. , 1999, JAMA.

[25]  J. West,et al.  Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer , 2015, Annals of Surgical Oncology.

[26]  Sylvia K Plevritis,et al.  Online tool to guide decisions for BRCA1/2 mutation carriers. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  A. Neugut,et al.  Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Shannon K. McDonnell,et al.  EFFICACY OF BILATERAL PROPHYLACTIC MASTECTOMY IN WOMEN WITH A FAMILY HISTORY OF BREAST CANCER , 1999 .

[29]  V. Moyer Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. , 2014, Annals of internal medicine.

[30]  B. Ward,et al.  BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast‐ovarian cancer , 2009, Cancer.

[31]  A. Kurian,et al.  Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment , 2015, Current opinion in obstetrics & gynecology.

[32]  A. Neugut,et al.  Cost-Effectiveness of Preventive Strategies for Women with a BRCA1 or a BRCA2 Mutation , 2006, Annals of Internal Medicine.

[33]  F. Johnson,et al.  Valuations of genetic test information for treatable conditions: the case of colorectal cancer screening. , 2014, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[34]  C. Flowers,et al.  Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population , 2009, BMC health services research.

[35]  Elisa F. Long,et al.  Cost-effectiveness of Universal BRCA1/2 Screening: Evidence-Based Decision Making. , 2015, JAMA oncology.

[36]  Colin C Pritchard,et al.  Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  R. McGaha,et al.  Breast cancer recurrence in older women five to ten years after diagnosis , 2010 .

[38]  Giovanni Parmigiani,et al.  Meta-analysis of BRCA1 and BRCA2 penetrance. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  L. Shulman Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population , 2011 .

[40]  S. Plevritis,et al.  A Simulation Model to Predict the Impact of Prophylactic Surgery and Screening on the Life Expectancy of BRCA1 and BRCA2 Mutation Carriers , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[41]  Graham A. Colditz,et al.  Breast cancer risk reduction, version 2.2015 clinical practice guidelines in oncology clinical practice guidelines in oncology , 2015 .

[42]  R. Goldbohm,et al.  Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease , 2001, The Lancet.

[43]  Karla Bowles,et al.  Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next‐generation sequencing with a 25‐gene panel , 2015, Cancer.

[44]  K. Noyes,et al.  Cost-effectiveness of testing for breast cancer susceptibility genes. , 2009, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[45]  M. Tischkowitz,et al.  Opportunities and challenges of next‐generation DNA sequencing for breast units , 2014, The British journal of surgery.

[46]  Yuya Kobayashi,et al.  Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Eric J Feuer,et al.  Projections of the cost of cancer care in the United States: 2010-2020. , 2011, Journal of the National Cancer Institute.