title: Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
abstract: BACKGROUND
  Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.
  
  
  OBJECTIVE
  To estimate risk and mortality reduction stratified by mutation and prior cancer status.
  
  
  METHODS
  Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.
  
  
  METHODS
  Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.
  
  
  RESULTS
  No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).
  
  
  CONCLUSIONS
  Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
authors.affiliation: Abramson Cancer Center and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Ellen
authors.initials: E
authors.lastname: Matloff
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pichert
authors.forename: Laura
authors.initials: L
authors.lastname: Van t'veer
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weitzel
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Rubinstein
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Gail
authors.initials: G
authors.lastname: Tomlinson
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D002423:Cause of Death; D005187:Fallopian Tubes / Q000601:surgery; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D010052:Ovariectomy; D011446:Prospective Studies; D012306:Risk
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