title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. rebbeck@mail.med.upenn.edu
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Noah D
authors.initials: ND
authors.lastname: Kauff
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control*; D016022:Case-Control Studies; D015331:Cohort Studies; D005187:Fallopian Tubes / Q000601:surgery*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D011322:Primary Prevention / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior