title: Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.
abstract: BACKGROUND
  In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes.
  
  
  METHODS
  We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models.
  
  
  RESULTS
  We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%).
  
  
  CONCLUSIONS
  Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. hartmann.lynn@mayo.edu
authors.forename: L C
authors.initials: LC
authors.lastname: Hartmann
authors.forename: T A
authors.initials: TA
authors.lastname: Sellers
authors.forename: D J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: T S
authors.initials: TS
authors.lastname: Frank
authors.forename: C L
authors.initials: CL
authors.lastname: Soderberg
authors.forename: D L
authors.initials: DL
authors.lastname: Sitta
authors.forename: M H
authors.initials: MH
authors.lastname: Frost
authors.forename: C S
authors.initials: CS
authors.lastname: Grant
authors.forename: J H
authors.initials: JH
authors.lastname: Donohue
authors.forename: J E
authors.initials: JE
authors.lastname: Woods
authors.forename: S K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: C W
authors.initials: CW
authors.lastname: Vockley
authors.forename: A
authors.initials: A
authors.lastname: Deffenbaugh
authors.forename: F J
authors.initials: FJ
authors.lastname: Couch
authors.forename: R B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008408:Mastectomy; D009154:Mutation