title: Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity.
abstract: BACKGROUND
  Patients with BRCA-associated ovarian cancer (OC) have a survival advantage over those with sporadic OC. To further explore this, we examined the impact of prognostic factors on disease-free survival (DFS) and overall survival (OS) in patients with known BRCA mutation status.
  
  
  METHODS
  We reviewed stage III-IV OC patients treated at our institution between 1 December 1996 and 30 September 2006 and also tested on protocol for BRCA mutations. Impact on DFS and OS was determined by Kaplan-Meier analysis and a Cox proportional hazards model.
  
  
  RESULTS
  Of the 110 patients, 36 had deleterious BRCA mutations [BRCA (+)] and 74 were BRCA wild type [BRCA(-)]. Thirty-one of 36 (86%) BRCA (+) and 60 of 74 (81%) BRCA (-) patients were platinum sensitive (P = 0.60). Median OS was longer for BRCA (+) patients (not reached versus 67.8 months; P = 0.02), but DFS was similar (26.9 versus 24.0, P = 0.3). On multivariate analysis, OS correlated with primary platinum sensitivity [HR = 0.15; 95% CI (confidence interval) 0.06-0.34] and BRCA (+) mutation status (HR = 0.33; 95% CI 0.12-0.86).
  
  
  CONCLUSIONS
  BRCA mutation status predicted OS independent of primary platinum sensitivity, suggesting that underlying tumor biology contributes to disease outcome and may be worthy of consideration in future clinical trial design.
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine; Clinical Genetics Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: D J
authors.initials: DJ
authors.lastname: Gallagher
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: J A
authors.initials: JA
authors.lastname: Konner
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: K M
authors.initials: KM
authors.lastname: Bell-McGuinn
authors.affiliation: Clinical Genetics Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: J
authors.initials: J
authors.lastname: Bhatia
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: P
authors.initials: P
authors.lastname: Sabbatini
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: C A
authors.initials: CA
authors.lastname: Aghajanian
authors.affiliation: Clinical Genetics Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Barakat
authors.affiliation: Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine.
authors.forename: D R
authors.initials: DR
authors.lastname: Spriggs
authors.affiliation: Clinical Genetics Service, Division of Solid Tumor Oncology, Department of Medicine; Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA. Electronic address: kauffn@mskcc.org.
authors.forename: N D
authors.initials: ND
authors.lastname: Kauff
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D010984:Platinum / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010984:Platinum