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Original Contribution
September 1, 2010

Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality

Author Affiliations

Author Affiliations: Abramson Cancer Center (Drs Domchek and Rebbeck), Department of Medicine (Dr Domchek), and Center for Clinical Epidemiology and Biostatistics (Ms Friebel and Dr Rebbeck), University of Pennsylvania School of Medicine, Philadelphia; Division of Special Gynecology, Medical University of Vienna, Vienna, Austria (Dr Singer); Department of Clinical Genetics, St Mary's Hospital, Manchester, England (Dr Evans); Department of Preventive Medicine, Creighton University, Omaha, Nebraska (Dr Lynch); Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (Dr Isaacs); Dana Farber Cancer Institute, Boston, Massachusetts (Dr Garber); Epidemiology Division, School of Medicine, University of California, Irvine (Dr Neuhausen); Cancer Genetic Counseling Program, Yale University, New Haven, Connecticut (Ms Matloff); Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, England (Dr Eeles); Guys and St Thomas Foundation Trust, London, England (Dr Pichert); Netherlands Cancer Institute, Amsterdam, the Netherlands (Dr Van t’veer); Beth Israel Deaconess Medical Center, Boston, Massachusetts (Dr Tung); City of Hope National Medical Center, Duarte, California (Dr Weitzel); Mayo Clinic College of Medicine, Rochester, Minnesota (Dr Couch); NorthShore University HealthSystem, Evanston, Illinois (Dr Rubinstein); University of Chicago Medical Center, Chicago, Illinois (Drs Rubinstein and Olopade); Jonsson Comprehensive Cancer Center, University of California, Los Angeles (Dr Ganz); Fox Chase Cancer Center, Philadelphia, Pennsylvania (Dr Daly); Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio (Dr Tomlinson); Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina (Dr Schildkraut); and Baylor-Charles A. Sammons Cancer Center, Dallas, Texas (Dr Blum).

JAMA. 2010;304(9):967-975. doi:10.1001/jama.2010.1237
Abstract

Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.

Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status.

Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.

Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.

Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).

Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.

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