COMMENTARY

Surgical Intervention to Reduce the Risk for Breast and Ovarian Cancer in BRCA Carriers

Maurie Markman, MD

Disclosures

April 07, 2010

Meta-Analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-Oophorectomy in BRCA1 or BRCA2 Mutation Carriers

Rebbeck TR, Kauff ND, Domchek SM
J Natl Cancer Inst. 2009;101:80-87

Survival Analysis of Cancer Risk Reduction Strategies for BRCA1/2 Mutation Carriers

Kurian AW, Sigal BM, Plevritis SK
J Clin Oncol. 2010;2:222-231

Summary

In 2009, Rebbeck and colleagues conducted a meta-analysis of 10 previously reported individual studies evaluating the clinical utility of a risk-reducing salpingo-oophorectomy in the prevention of cancers of the breast and ovary in women with known BRCA1 and BRCA2 mutations. Their analysis revealed that the surgery resulted in an approximate 50% reduction in the subsequent development of breast cancer in women with either a BRCA1 or a BRCA2 genetic abnormality. In addition, the procedure was revealed to decrease the risk for ovarian or fallopian tube cancers by approximately 80%.

Due to limited patient numbers, it was not possible to determine the relative improvement in the risk for ovarian/fallopian tube cancers based whether there was a mutation in BRCA1 vs BRCA2. Nevertheless, consistency in the overall impact of risk-reducing salpingo-oophorectomy across the various studies analyzed was noted by the investigators as adding an important element of support for the study's conclusions.

Building on this work, in a more recent provocative decision analysis employing a variety of possible screening and possible time points for the performance of prophylactic surgery, Kurian and colleagues suggest that the most effective strategy in both BRCA1 and BRCA2 mutation carriers is prophylactic mastectomy and oophorectomy undertaken at age 40. The data presented in this article suggest that prophylactic surgery performed before age 40 would add little to the benefits associated with this intervention.

Viewpoint

Data from these 2 articles add to the growing body of evidence that the performance of a bilateral salpingo-oophorectomy will substantially reduce the risk for breast or ovarian/fallopian tube cancer in women with a known high genetic risk. In the case of breast cancer, the degree of risk reduction is approximately 50%, while that for ovarian/fallopian tube cancer is 80%.

However, a number of important questions remain, including: (a) the age at which such procedures should be undertaken in individual patients; (b) the extent of risk reduction observed over a lifetime of 30-50+ years vs a more limited 10- or 15-year follow-up; and (c) the overall negative impact associated with early surgical menopause (eg, quality-of-life concerns, risk for accelerated development of osteoporosis, and cardiac abnormalities).

At the same time, women with BRCA1 and BRCA2 mutations, along with their physicians, need to consider other strategies that have been documented, or strongly suggested, to possibly play a relevant role in reducing cancer risk, including screening and chemoprevention for breast cancer, and the use of oral contraceptives and the performance of a bilateral tubal ligation for ovarian cancer.

Abstract

Abstract

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