title: Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers.
abstract: BACKGROUND
  The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers.
  
  
  METHODS
  We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth.
  
  
  RESULTS
  We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery.
  
  
  CONCLUSIONS
  Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.
authors.affiliation: T. R. Rebbeck, A. Eisen, B. L. Weber, Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. trebbeck@cceb.med.upenn.edu
authors.forename: T R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: A M
authors.initials: AM
authors.lastname: Levin
authors.forename: A
authors.initials: A
authors.lastname: Eisen
authors.forename: C
authors.initials: C
authors.lastname: Snyder
authors.forename: P
authors.initials: P
authors.lastname: Watson
authors.forename: L
authors.initials: L
authors.lastname: Cannon-Albright
authors.forename: C
authors.initials: C
authors.lastname: Isaacs
authors.forename: O
authors.initials: O
authors.lastname: Olopade
authors.forename: J E
authors.initials: JE
authors.lastname: Garber
authors.forename: A K
authors.initials: AK
authors.lastname: Godwin
authors.forename: M B
authors.initials: MB
authors.lastname: Daly
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: S L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
mesh_terms: D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control / Q000601:surgery*; D016022:Case-Control Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D016017:Odds Ratio; D010052:Ovariectomy; D012042:Registries; D012306:Risk; D011795:Surveys and Questionnaires; D013997:Time Factors