title: Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer.
abstract: OBJECTIVE
  • To investigate the relationship between BRCA mutation status and response to taxane-based chemotherapy, since BRCA mutation carriers with prostate cancer appear to have worse survival than non-carriers and docetaxel improves survival in patients with castration-resistant prostate cancer.
  
  
  METHODS
  • We determined BRCA mutation prevalence in 158 Ashkenazi Jewish (AJ) men with castration-resistant prostate cancer. Clinical data were collected as part of an institutional prostate cancer research database and through additional medical record review. • Clinical records and DNA samples were linked through a unique identifier, anonymizing the samples before genetic testing for the AJ BRCA1/2 founder mutations. • Response to taxane-based therapy was defined by the prostate-specific antigen nadir within 12 weeks of therapy.
  
  
  RESULTS
  • In all, 88 men received taxane-based treatment, seven of whom were BRCA carriers (three BRCA1, four BRCA2; 8%). Initial response to taxane was available for all seven BRCA carriers and for 69 non-carriers. • Overall, 71% (54/76) of patients responded to treatment, with no significant difference between carriers (57%) and non-carriers (72%) (absolute difference 15%; 95% confidence interval -23% to 53%; P= 0.4). • Among patients with an initial response, the median change in prostate-specific antigen was similar for BRCA carriers (-63%, interquartile range -71% to -57%) and non-carriers (-60%, interquartile range -78% to -35%) (P= 0.6). • At last follow-up, all seven BRCA carriers and 49 non-carriers had died from prostate cancer. One BRCA2 carrier treated with docetaxel plus platinum survived 37 months.
  
  
  CONCLUSIONS
  • In this small, hypothesis-generating study approximately half of BRCA carriers had a prostate-specific antigen response to taxane-based chemotherapy, suggesting that it is an active therapy in these individuals.
authors.affiliation: Genitourinary Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gallagher
authors.forename: Angel M
authors.initials: AM
authors.lastname: Cronin
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Jasmine
authors.initials: J
authors.lastname: Bhatia
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Mark E
authors.initials: ME
authors.lastname: Robson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane