title: Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.
abstract: BACKGROUND
  Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women.
  
  
  METHODS
  We conducted a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance program at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women eventually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastectomy was modeled as a time-dependent covariate.
  
  
  RESULTS
  No cases of breast cancer were observed after prophylactic mastectomy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer among all women in the surveillance group was 17+/-7 percent. On the basis of an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expected cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80).
  
  
  CONCLUSIONS
  In women with a BRCA1 or BRCA2 mutation, prophylactic bilateral total mastectomy reduces the incidence of breast cancer at three years of follow-up.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: B
authors.initials: B
authors.lastname: van Geel
authors.forename: W L
authors.initials: WL
authors.lastname: van Putten
authors.forename: S C
authors.initials: SC
authors.lastname: Henzen-Logmans
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.forename: M B
authors.initials: MB
authors.lastname: Menke-Pluymers
authors.forename: C C
authors.initials: CC
authors.lastname: Bartels
authors.forename: L C
authors.initials: LC
authors.lastname: Verhoog
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: M F
authors.initials: MF
authors.lastname: Niermeijer
authors.forename: C T
authors.initials: CT
authors.lastname: Brekelmans
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D000328:Adult; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control* / Q000601:surgery; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D015413:Mastectomy, Simple; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors