title: Improved survival in non-Ashkenazi Jewish ovarian cancer patients with BRCA1 and BRCA2 gene mutations.
abstract: OBJECTIVE
  Previous studies report a survival advantage in ovarian cancer patients with Ashkenazi Jewish (AJ) breast cancer gene (BRCA) founder mutations. The purpose of this study was to determine if this association exists in patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations. We also sought to account for "survival bias" by minimizing lead time that may exist between diagnosis and genetic testing.
  
  
  METHODS
  Patients with stage III/IV ovarian cancer and a non-AJ BRCA mutation, seen between January 1996 and July 2007, were identified from eight institutions. Patients with sporadic ovarian cancer were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. Progression-free (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Fisher's exact test and chi-square were also used for analysis.
  
  
  RESULTS
  Ninety-five advanced stage ovarian cancer patients with non-AJ BRCA mutations and 183 sporadic controls were analyzed. Compared to sporadic ovarian cancer patients, non-AJ BRCA patients had longer PFS (27.9 months vs. 17.9 months, HR 0.61 [95% CI 0.43-0.86]) and OS (101.7 months vs. 54.3 months, HR 0.43 [95% CI 0.27-0.68]). BRCA status was an independent predictor of PFS and OS.
  
  
  CONCLUSIONS
  This multicenter study demonstrates a significant survival advantage in advanced stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. This improved survival was evident when accounting for the "survival bias" that coincides with genetic testing.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-3721, USA. khlu@mdanderson.org
authors.forename: Robin A
authors.initials: RA
authors.lastname: Lacour
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Westin
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Meyer
authors.forename: Shana N
authors.initials: SN
authors.lastname: Wingo
authors.forename: John O
authors.initials: JO
authors.lastname: Schorge
authors.forename: Rebecca
authors.initials: R
authors.lastname: Brooks
authors.forename: David
authors.initials: D
authors.lastname: Mutch
authors.forename: Ashley
authors.initials: A
authors.lastname: Molina
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sutphen
authors.forename: Mack
authors.initials: M
authors.lastname: Barnes
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Elder
authors.forename: Deanna
authors.initials: D
authors.lastname: Teoh
authors.forename: C Bethan
authors.initials: CB
authors.lastname: Powell
authors.forename: Veena
authors.initials: V
authors.lastname: Choubey
authors.forename: Stephanie
authors.initials: S
authors.lastname: Blank
authors.forename: Heather R
authors.initials: HR
authors.lastname: Macdonald
authors.forename: Mark F
authors.initials: MF
authors.lastname: Brady
authors.forename: Diana L
authors.initials: DL
authors.lastname: Urbauer
authors.forename: Diane
authors.initials: D
authors.lastname: Bodurka
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology; D016016:Proportional Hazards Models; D015996:Survival Rate