Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers

Abstract

Background: Risk-reducing salpingo-oophorectomy (RRSO) is widely used by carriers of BRCA1 or BRCA2 (BRCA1/2) mutations to reduce their risks of breast and ovarian cancer. To guide women and their clinicians in optimizing cancer prevention strategies, we summarized the magnitude of the risk reductions in women with BRCA1/2 mutations who have undergone RRSO compared with those who have not.

Methods: All reports of RRSO and breast and/or ovarian or fallopian tube cancer in BRCA1/2 mutation carriers published between 1999 and 2007 were obtained from a PubMed search. Hazard ratio (HR) estimates were identified directly from the original articles. Pooled results were computed from nonoverlapping studies by fixed-effects meta-analysis.

Results: Ten studies investigated breast or gynecologic cancer outcomes in BRCA1/2 mutation carriers who had undergone RRSO. Breast cancer outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers, four of BRCA1 mutation carriers, and three of BRCA2 mutation carriers. Gynecologic cancer outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers and one of BRCA1 mutation carriers. RRSO was associated with a statistically significant reduction in risk of breast cancer in BRCA1/2 mutation carriers (HR = 0.49; 95% confidence interval [CI] = 0.37 to 0.65). Similar risk reductions were observed in BRCA1 mutation carriers (HR = 0.47; 95% CI = 0.35 to 0.64) and in BRCA2 mutation carriers (HR = 0.47; 95% CI = 0.26 to 0.84). RRSO was also associated with a statistically significant reduction in the risk of BRCA1/2-associated ovarian or fallopian tube cancer (HR = 0.21; 95% CI = 0.12 to 0.39). Data were insufficient to obtain separate estimates for ovarian or fallopian tube cancer risk reduction with RRSO in BRCA1 or BRCA2 mutation carriers.

Conclusion: The summary estimates presented here indicate that RRSO is strongly associated with reductions in the risk of breast, ovarian, and fallopian tube cancers and should provide guidance to women in planning cancer risk reduction strategies.

Figure 1

Forest plots of relative risk (RR) estimates for risk reduction associated with risk-reducing salpingo-oophorectomy (RRSO). A) Ovarian cancer risk reduction in BRCA1/2 mutation carriers. B) Breast cancer risk reduction in BRCA1/2 mutation carriers. C) Breast cancer risk reduction in BRCA1 mutation carriers. D) Breast cancer risk reduction in BRCA2 mutation carriers. The box sizes reflect the relative sample sizes of the individual studies; horizontal lines represent 95% confidence intervals (CIs). Diamonds represent the pooled point estimate and 95% confidence intervals. Vertical dashed lines represent the pooled relative risk estimate. Estimates less than a value of 1.0 suggest a favorable reduction in cancer risk associated with RRSO.