title: Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer.
abstract: BACKGROUND
  Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated.
  
  
  OBJECTIVE
  To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT).
  
  
  METHODS
  Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo.
  
  
  METHODS
  Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations.
  
  
  CONCLUSIONS
  A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (p<0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than in carriers (96%, 76%, and 61%, respectively; p<0.001). Multivariate analysis confirmed BRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p=0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p=0.016).
  
  
  CONCLUSIONS
  BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa.
  
  
  RESULTS
  Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy.
authors.affiliation: Prostate Cancer Unit, Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: ecastro@cnio.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Castro
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Chee
authors.initials: C
authors.lastname: Goh
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leongamornlert
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Saunders
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Tymrakiewicz
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Tokhir
authors.initials: T
authors.lastname: Dadaev
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Koveela
authors.initials: K
authors.lastname: Govindasami
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Guy
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Ellis
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Debra
authors.initials: D
authors.lastname: Frost
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bancroft
authors.affiliation: West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Tischkowitz
authors.affiliation: Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St. James's Hospital, Dublin, Ireland.
authors.forename: M John
authors.initials: MJ
authors.lastname: Kennedy
authors.affiliation: Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Eason
authors.affiliation: Department of Clinical Genetics, Royal Devon and Exeter Hospital, Exeter, UK.
authors.forename: Carole
authors.initials: C
authors.lastname: Brewer
authors.affiliation: Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.affiliation: Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Davidson
authors.affiliation: University of Southampton Faculty of Medicine, Southampton University Hospitals NHS Trust, Southampton, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.affiliation: South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Porteous
authors.affiliation: Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Douglas
authors.affiliation: Yorkshire Regional Genetics Service, Leeds, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Adlard
authors.affiliation: Clinical Genetics Department, St. Michael's Hospital, Bristol, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Donaldson
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Prostate Cancer Unit, Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Electronic address: dolmos@cnio.es.
authors.forename: David
authors.initials: D
authors.lastname: Olmos
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D010641:Phenotype; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: BRCA1; BRCA2; Homologous repair; Prognostic factor; Prostate cancer; Prostatectomy; Radiotherapy