{"entity":{"id":"paper-castro-germline-brca-prostate-outcomes-jco-2013","kind":"paper","name":"Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer","aka":[],"tldr":"Comparing 79 men who inherited a BRCA fault with 1,940 who did not showed the carriers' cancers were higher grade, more often spread at diagnosis, and shortened life by years.","summary":"The tumour features and outcomes of 2,019 men with prostate cancer were analysed, 18 BRCA1 carriers, 61 BRCA2 carriers and 1,940 non-carriers. Prostate cancers in germline BRCA1 or BRCA2 carriers were more often Gleason 8 or higher, T3 or T4 stage, node-positive and metastatic at diagnosis. Cause-specific survival was significantly longer in non-carriers, 15.7 against 8.6 years, with a multivariable hazard ratio of 1.8. For localised disease at presentation, five-year cause-specific survival was 96% in non-carriers against 82% in carriers and five-year metastasis-free survival 93% against 77%. Subgroup analyses confirmed the poor outcomes in BRCA2 carriers, while the role of BRCA1 could not be defined because of the limited size of that subgroup.","asOf":"2026-09-25","links":[{"label":"Castro et al., J Clin Oncol 2013: germline BRCA1 and BRCA2 mutations and outcome in 2,019 men with prostate cancer","url":"https://doi.org/10.1200/JCO.2012.43.1882"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23569316/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ddr"],"terms":["germline-vs-somatic","gbrca-mutation","gleason-grade-group","hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.43.1882","pmid":"23569316","authors":"Castro E, Goh C, Olmos D, et al.","paperType":"observational","findings":["Carriers more often Gleason 8 or above, T3/T4, node-positive and metastatic at diagnosis.","Cause-specific survival 15.7 years in non-carriers against 8.6 years in carriers, hazard ratio 1.8.","Five-year cause-specific survival in localised disease 96% against 82%, metastasis-free survival 93% against 77%.","The effect was confirmed for BRCA2; BRCA1 could not be resolved with 18 carriers."],"whatItMeans":"It established that an inherited BRCA2 mutation changes the disease and not only the treatment options, which is why a carrier's localised disease is generally treated more intensively and watched more closely rather than put on surveillance.","caveats":["These are cohort figures and not a personal prognosis.","Predates PARP inhibitors, hormone intensification in castration-sensitive disease and PSMA PET staging, all of which change outcomes.","Carriers were identified through family-cancer programmes, which selects for stronger family histories."],"changedPractice":true,"participants":2019},"route":"/key-papers/paper-castro-germline-brca-prostate-outcomes-jco-2013/","neighbours":{"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"pathway":[{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"gleason-grade-group","kind":"term","name":"Gleason score / Grade Group","route":"/terms/gleason-grade-group/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"}]}}