ArticleEBioMedicine2023
BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype.
Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Real-World Outcomes of Olaparib Treatment in Japanese Patients With Metastatic Castration-Resistant Prostate Cancer Harboring BRCA Pathogenic or Likely Pathogenic Variants.International journal of urology : official journal of the Japanese Urological Association · 2026Observational
- Serum CCL2 and CCL7 in Prostate Cancer: Evaluation of Their Diagnostic Utility in Comparison with Benign Prostatic Hyperplasia and Healthy Controls.International journal of molecular sciences · 2026Article
- Rucaparib - drug evaluation: a PARP inhibitor for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer.Future oncology (London, England) · 2026Review
- Functional footprints of homologous recombination deficiency in prostate cancer revealed by ctDNA fragmentation and transcription factor accessibility.British journal of cancer · 2026Article
- Variable cellular and radiobiological effects of [Journal of experimental & clinical cancer research : CR · 2026Article
- Review
- Male infertility and the risk of developing prostate cancer: a bidirectional two-sample Mendelian randomization study.European journal of medical research · 2025Article
- Homologous recombination repair genetic testing variables and diagnostic paths for prostate cancer patients: a multicenter cohort study.The oncologist · 2025Observational
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- Article
- Association of Homologous Recombination Repair Alterations with Outcomes in Patients with Metastatic Hormone-Sensitive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- BRCA Mutation Testing in Men With Metastatic Castration-Resistant Prostate Cancer: Practical Guidance for Australian Clinical Practice.Asia-Pacific journal of clinical oncology · 2025Review
- Droplet Digital PCR Improves Detection ofInternational journal of molecular sciences · 2025Article
- Two Japanese patients with metastatic castration-resistant prostate cancer with somatic biallelicInternational cancer conference journal · 2025Article
- Deep targeted sequencing of circulating tumor DNA to inform treatment in patients with metastatic castration-resistant prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Unravelling targeted therapy in prostate cancer: from molecular mechanisms to translational opportunities.Frontiers in cell and developmental biology · 2025Review
- Article
- Adaptive Treatment of Metastatic Prostate Cancer Using Generative Artificial Intelligence.Clinical Medicine Insights. Oncology · 2025Review
- The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundGenomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes.
methodsTargeted sequencing was performed on 407 plasma samples from 375 men with mCRPC. Using the CLIA-certified PredicineCARE™ cell-free DNA (cfDNA) assay, pathogenic alterations in 152 key genes (including 27 DDR-related genes) were assessed, as was the presence and mechanisms of biallelic loss in BRCA2.
findingsAt least one DDR alteration was present in 34.5% (129/375) of patients (including monoallelic alterations). The most frequently altered DDR genes were BRCA2 (19%), ATM (13%), FANCA (5%), CHEK2 (5%) and BRCA1 (3%). Patients with BRCA alterations, especially BRCA2, had significantly worse progression-free survival (PFS) (Hazard ratio (HR) 3.3 [95% CI 1.9-6.0]; Cox regression p < 0.001), overall survival (HR 2.2 [95% CI 1.1-4.5]; Cox regression p = 0.02) and PSA response rates to androgen receptor (AR) pathway inhibitors (32% vs 60%, chi-square p = 0.02). BRCA-deficient tumours were also enriched for alterations within multiple genes including in the AR and PI3K pathways. Zygosity of BRCA2 alterations had no discernible impact on clinical outcomes, with similarly poor PFS for monoallelic vs biallelic loss (median 3.9 months vs 3.4 months vs copy neutral 9.8 months).
interpretationThese data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected. Enrichment of actionable genomic alterations in cfDNA from BRCA-deficient mCRPC may support rational co-targeting strategies in future clinical trials.
fundingSeveral funding sources have supported this study. A full list is provided in the Acknowledgments. No funding was received from Predicine, Inc. during the conduct of the study.
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