title: Implications of High Rates of Metastatic Prostate Cancer in BRCA2 Mutation Carriers.
abstract: Patients with germline BRCA2 gene mutations (BRCA2mut) have more aggressive prostate cancer. Analysis of all reported germline BRCA2mut prostate cancer cases allows better understanding of the clinicopathologic features and survival outcomes of these men.
  
  
  
  A systematic review was performed with the MEDLINE database to capture articles evaluating clinicopathologic characteristics of men with BRCA2mut associated prostate cancer. Inclusion criteria were at least five subjects, confirmation of BRCA2mut status, and data for at least 2 clinical parameters of disease. Meta-analysis was performed on outcomes data. Chi-squared tests were used to compare disease features among men undergoing formal versus ad hoc screening, as well as an age of diagnosis less than versus greater than 65 years. Rates of metastatic disease among BRCA2mut cases were compared to rates among non-carrier control subjects and the general population using the SEER database.
  
  
  
  Twelve out of 289 studies met our inclusion criteria, representing 261 BRCA2mut men. Among carriers, the median age at diagnosis was 62 years and median PSA was 15 ng/dl with 95% of men having a PSA>3. Over 40% of BRCA2mut patients had T3/T4 disease and over 25% were metastatic at presentation. Survival was worse in BRCA2mut men with prostate cancer when compared to non-BRCA2mut subjects. BRCA2mut carriers had significantly higher rates of metastatic disease (18%) versus non-carrier controls (8%) and the SEER population (4%).
  
  
  
  BRCA2mut carriers are more likely to have poor risk of prostate cancer at presentation and exhibit worse oncologic outcomes relative to non-carriers, including a fourfold increase in metastatic disease. Younger men and those undergoing formal screening present with less advanced disease which supports a need for earlier identification and screening protocols. Additionally, this population may benefit from alternative therapeutic paradigms. Prostate 76:1135-1145, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gleicher
authors.affiliation: Departments of Urology and Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York.|Department of Urology, SUNY University of Buffalo, Buffalo, New York.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Kauffman
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, New York.|Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kotula
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Vourganti
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D017430:Prostate-Specific Antigen
keywords: BRCA2; aggressive; metastatic; prostate; screening