title: Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer.
abstract: BACKGROUND
  Multiple observational studies have suggested that breast cancer gene (BRCA)-associated ovarian cancers have improved survival compared with BRCA-negative ovarian cancers. However, most of those studies combined BRCA1 and BRCA2 patients or evaluated only BRCA1 patients. The objective of the current study was to examine whether BRCA1-associated and BRCA2-associated ovarian cancers were associated with different outcomes.
  
  
  METHODS
  This was a single-institution, retrospective analysis of patients who had a new diagnosis of histologically confirmed stage III or IV serous ovarian, fallopian tube, or primary peritoneal cancer between January 1, 1996 and February 1, 2011 and who underwent BRCA mutation testing on 1 of 2 institutional review board-approved follow-up studies. Patients who had been tested for BRCA mutations beyond 24 months of diagnosis were excluded from analysis to minimize selection bias from including patients who were referred for genetic testing because of long survival.
  
  
  RESULTS
  Data from 190 patients (143 BRCA-negative patients, 30 BRCA1-positive patients, and 17 BRCA2-positive patients) were analyzed. During the study period, 73 deaths were observed (60 BRCA-negative patients, 10 BRCA1-positive patients, 3 BRCA2-positive patients). The median follow-up for the remaining 117 survivors was 2.5 years. At 3 years, 69.4%, 90.7%, and 100% of BRCA-negative patients, BRCA1-positive patients, and BRCA2-positive patients were alive, respectively. On univariate analysis, age, BRCA2 mutations, debulking status, and type of first-line therapy (intravenous or intraperitoneal) were significant predictors of overall survival. On multivariate analysis, BRCA2 mutations (hazard ratio, 0.20; 95% confidence interval, 0.06-0.65; P = .007), but not BRCA1 mutations (hazard ratio, 0.70; 95% confidence interval, 0.36-1.38; P = .31), predicted for improved overall survival compared with BRCA-negative patients. When carriers of BRCA2 mutations were directly compared with carriers of BRCA1 mutations, BRCA2 mutations appeared to confer improved overall survival (hazard ratio, 0.29; 95% confidence interval, 0.08-1.05; P = .060), although this finding did not reach significance.
  
  
  CONCLUSIONS
  The current data suggests that BRCA2 mutations confer an overall survival advantage compared with either being BRCA-negative or having a BRCA1 mutation in high-grade serous ovarian cancer. This finding may have important implications for clinical trial design.
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hyman
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Grisham
authors.forename: Angela G
authors.initials: AG
authors.lastname: Arnold
authors.forename: Mary F
authors.initials: MF
authors.lastname: Phillips
authors.forename: Jasmine
authors.initials: J
authors.lastname: Bhatia
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: Noah D
authors.initials: ND
authors.lastname: Kauff
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality