title: Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study.
abstract: OBJECTIVE
  To compare breast cancer prognosis in BRCA1 and BRCA2 mutation carriers with that in patients with sporadic disease.
  
  
  METHODS
  An international population-based cohort study was conducted in Canada, the United States, and Australia of 3,220 women with incident breast cancer diagnosed between 1995 and 2000 and observed prospectively. Ninety-three had BRCA1 mutations; 71, BRCA2 mutations; one, both mutations; 1,550, sporadic breast cancer; and 1,505, familial breast cancer (without known BRCA1 or BRCA2 mutation). Distant recurrence and death were analyzed.
  
  
  RESULTS
  Mean age at diagnosis was 45.3 years; mean follow-up was 7.9 years. Risks of distant recurrence and death did not differ significantly between BRCA1 mutation carriers and those with sporadic disease in univariable and multivariable analyses. Risk of distant recurrence was higher for BRCA2 mutation carriers compared with those with sporadic disease in univariable analysis (hazard ratio [HR], 1.63; 95% CI, 1.02 to 2.60; P = .04). Risk of death was also higher in BRCA2 carriers in univariable analysis (HR, 1.81; 95% CI, 1.15 to 2.86; P = .01). After adjustment for age, tumor stage and grade, nodal status, hormone receptors, and year of diagnosis, no differences were observed for distant recurrence (HR, 1.00; 95% CI, 0.62 to 1.61; P = 1.00) or death (HR, 1.12; 95% CI, 0.70 to 1.79; P = .64).
  
  
  CONCLUSIONS
  Outcomes of BRCA1 mutation carriers were similar to those of patients with sporadic breast cancer. Worse outcomes in BRCA2 mutation carriers in univariable analysis seem to reflect the presence of more adverse tumor characteristics in these carriers. Similar outcomes were identified in BRCA2 carriers and those with sporadic disease in multivariable analyses.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario. pgoodwin@mtsinai.on.ca
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Goodwin
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.forename: Dee W
authors.initials: DW
authors.lastname: West
authors.forename: Marguerite
authors.initials: M
authors.lastname: Ennis
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: Michael L
authors.initials: ML
authors.lastname: Friedlander
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Carmel
authors.initials: C
authors.lastname: Apicella
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Teri A
authors.initials: TA
authors.lastname: Longacre
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002170:Canada; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007391:International Cooperation; D007585:Jews / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D014481:United States