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Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

From the Faculty of Nursing and the Centre for Research on Women's Health, and Sunnybrook and Women's College Health Sciences Centre, University of Toronto; Toronto Sunnybrook Regional Cancer Centre, Toronto; Epidemiology Research Unit, Centre Hospitalier de Université de Montreal (CHUM); Program in Cancer Genetics, McGill University, Montreal; British Columbia Cancer Agency, Vancouver; Hamilton Regional Cancer Centre, Hamilton, Canada; Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE; Beth Israel Deaconess Medical Center, Boston, MA; Department of Medicine, University of Chicago, Chicago, IL; Departments of Medicine and Genetics, Department of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA; Cancer Risk Program, UCSF Comprehensive Cancer Center, San Francisco, CA

Address reprint requests to Steven Narod, MD, Centre for Research on Women's Health, Women's College Hospital, 790 Bay St, Room 750, Toronto, Ontario, Canada M5G 1N8; e-mail: steven.narod{at}sw.ca

PURPOSE: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer.

PATIENTS AND METHODS: Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

RESULTS: The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers.

CONCLUSION: The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.

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

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