# Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer

Source: https://onco.cc/key-papers/paper-castro-germline-brca-prostate-outcomes-jco-2013/  
OnCo record `paper-castro-germline-brca-prostate-outcomes-jco-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of Clinical Oncology
- Year: 2013
- DOI: 10.1200/JCO.2012.43.1882
- Authors: Castro E, Goh C, Olmos D, et al.
- 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.
- What it means: 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.

## Sources

- Castro et al., J Clin Oncol 2013: germline BRCA1 and BRCA2 mutations and outcome in 2,019 men with prostate cancer: https://doi.org/10.1200/JCO.2012.43.1882
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23569316/

## Connected records

- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- pathways: [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Gleason score / Grade Group](https://onco.cc/terms/gleason-grade-group/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- biomarkers: [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/)

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