title: Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study.
abstract: BACKGROUND
  Bilateral prophylactic salpingo-oophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers.
  
  
  METHODS
  We identified a prospective cohort of 666 women with disease-associated germline mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. In our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for centre, mutation (BRCA1 vs BRCA2), and birth year.
  
  
  RESULTS
  In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2.4] in the BPSO group and 2.1 years [2.0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0.24 (95% CI 0.08-0.71), for breast-cancer-specific mortality was 0.10 (0.02-0.71), and for ovarian-cancer-specific mortality was 0.05 (0.01-0.46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0.28 [95% CI 0.10-0.74]), but not with breast-cancer-specific mortality (0.15 [0.02-1.18] or ovarian-cancer-specific mortality (0.23 [0.02-1.87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality.
  
  
  CONCLUSIONS
  If confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing.
authors.affiliation: Abramson Cancer Centre, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Theresa
authors.initials: T
authors.lastname: Wagner
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Ellen
authors.initials: E
authors.lastname: Matloff
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
authors.forename: Laura
authors.initials: L
authors.lastname: Van't Veer
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D005260:Female; D007839:Functional Laterality; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D010052:Ovariectomy; D011379:Prognosis; D011446:Prospective Studies