Journal of the National Cancer Institute Advance Access originally published online on January 13, 2009
JNCI Journal of the National Cancer Institute 2009 101(2):80-87; doi:10.1093/jnci/djn442
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Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers
Affiliations of authors: Center for Clinical Epidemiology and Biostatistics (TRR), Abramson Cancer Center (TRR, SMD), Department of Medicine (SMD), University of Pennsylvania School of Medicine, Philadelphia, PA; Clinical Genetics Service, Department of Medicine (NDK), Gynecology Service, Department of Surgery (NDK), Memorial Sloan-Kettering Cancer Center, New York, NY
Correspondence to: Timothy R. Rebbeck, PhD, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 904 Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104-6021 (e-mail: rebbeck{at}mail.med.upenn.edu).
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.
| CONTEXT AND CAVEATS Prior knowledge Risk-reducing salpingo-oophorectomy (RRSO)—the removal of the fallopian tubes and ovaries to reduce the risks of breast and ovarian cancer—is a cancer prevention strategy used by many women who carry germline mutations in the BRCA1 and/or BRCA2 genes (BRCA1/2). However, the magnitude of the risk reductions in women with BRCA1/2 mutations who have undergone RRSO compared with those who have not is unclear. Study design A fixed-effects meta-analysis of pooled results from 10 published reports of RRSO and the risks of breast and/or ovarian or fallopian tube cancer in BRCA1/2 mutation carriers. Contribution RRSO was found to be strongly associated with substantial reductions in the risks of breast, ovarian, and fallopian tube cancers among women who carry mutations in BRCA1 or BRCA2. Implications The summary risk reduction estimates should provide guidance to women in planning cancer risk reduction strategies. Limitations Data were not available to evaluate the effects of birth cohort, timing of surgery, or other factors that may influence the risk reduction estimates associated with RRSO. Women included in the studies were not representative of the general population. From the Editors
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Manuscript received May 28, 2008; revised October 22, 2008; accepted October 31, 2008.
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J Natl Cancer Inst 2009 101: 69.
J Natl Cancer Inst 2009 101: 69.
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