title: Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.
abstract: OBJECTIVE
  The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.
  
  
  METHODS
  Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.
  
  
  RESULTS
  Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8%; P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36%; P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30-0.76; P=0.002).
  
  
  CONCLUSIONS
  The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.
authors.affiliation: Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Metcalfe
authors.forename: S
authors.initials: S
authors.lastname: Gershman
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: P
authors.initials: P
authors.lastname: Ghadirian
authors.forename: N
authors.initials: N
authors.lastname: Tung
authors.forename: C
authors.initials: C
authors.lastname: Kim-Sing
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: S
authors.initials: S
authors.lastname: Domchek
authors.forename: J
authors.initials: J
authors.lastname: McLennan
authors.forename: A
authors.initials: A
authors.lastname: Eisen
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: B
authors.initials: B
authors.lastname: Rosen
authors.forename: P
authors.initials: P
authors.lastname: Sun
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D016017:Odds Ratio; D010052:Ovariectomy; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis