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Breast Cancer Risk Following Bilateral Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: An International Case-Control Study

From the Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada; Pomeranian Medical University, Szczecin, Poland; Daniel den Hoed Cancer Center and Erasmus University Medical Center, Rotterdam, Netherlands; Department of Cancer Genetics, Norwegian Radium Hospital, Oslo, Norway; Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE; Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Departments of Medicine and Genetics, University of Pennsylvania, Philadelphia, PA; Division of Epidemiology, Department of Medicine, University of California, Irvine, CA; Epidemiology Research Unit, CHUM Hôtel-Dieu, University of Montreal, and the Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada; Institute of Genetics, Rambam Medical Center, Haifa, and the Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, and the CHS National Cancer Control Center, Carmel Medical Center, Haifa, Israel; Private Trust for Breast Health, Division of Senology, University of Vienna, Austria; Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC; BC Cancer Agency, Vancouver, BC, and the London Regional Cancer Program, London, ON, and the Centre for Research in Women's Health, University of Toronto, ON, Canada

Address reprint requests to Steven A. Narod, Centre for Research in Women's Health, 790 Bay St, Toronto, Ontario, Canada M5G 1N8; e-mail: steven.narod{at}sw.ca

PURPOSE: The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery.

PATIENTS AND METHODS: We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use.

RESULTS: A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57).

CONCLUSION: Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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