{"doi":"10.1371/journal.pone.0239686","title":"Impact of mutations in homologous recombination repair genes on treatment outcomes for metastatic castration resistant prostate cancer","abstract":"INTRODUCTION: A significant proportion of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor mutations in homologous recombination (HR) repair genes, with some of these mutations associating with increased tumor susceptibility to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy. While mutations in some HR repair genes (e.g., BRCA1/2) have been associated with a more aggressive clinical course, prior studies correlating HR mutational status with treatment response to androgen receptor (AR) signaling inhibitors (ARSIs) or taxane-based chemotherapy have yielded conflicting results. METHODS: We conducted a single-center retrospective analysis to assess clinical outcomes to conventional, regulatory-approved therapies in mCRPC patients with somatic (monoallelic and biallelic) and/or germline HR repair mutations compared to patients without alterations as determined by clinical-grade next-generation sequencing assays. The primary endpoint was PSA30/PSA50 response, defined as ≥30%/≥50% prostate-specific antigen (PSA) reduction from baseline. Secondary endpoints of PSA progression-free survival (pPFS) and clinical/radiographic progression-free survival (crPFS) were estimated using Kaplan-Meier methods. RESULTS: A total of 90 consecutively selected patients were included in this analysis, of which 33 (37%) were identified to have HR repair gene mutations. Age, race, Gleason score, prior surgery, and receipt of prior radiation therapy were comparable between carriers and non-carriers. There was no evidence that PSA30/PSA50 differed by HR gene mutational status. Median pPFS and crPFS ranged 3-14 months across treatment modalities, but there was no evidence either differed by HR gene mutational status (all p>0.05). There was also no difference in outcomes between those with BRCA2 or PALB2 mutations (n = 17) compared to those without HR repair mutations. CONCLUSION: HR gene mutational status was associated with comparable clinical outcomes following treatment with ARSIs or taxane-based chemotherapy. Additional prospective studies are needed to confirm these findings.","journal":"PLoS ONE","year":2020,"id":88491,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":450041,"name":"Rigo I. Acevedo","orcid":null,"position":1,"is_corresponding":false},{"id":450042,"name":"Daniel M. Lim","orcid":null,"position":2,"is_corresponding":false},{"id":407350,"name":"Roman Gulati","orcid":"0000-0002-7592-6567","position":3,"is_corresponding":false},{"id":448835,"name":"Agnes Gawne","orcid":"0000-0002-9284-3608","position":4,"is_corresponding":false},{"id":255743,"name":"Alexandra Sokolova","orcid":"0000-0003-0821-6503","position":5,"is_corresponding":false},{"id":251018,"name":"Heather H. Cheng","orcid":"0000-0002-1365-0702","position":6,"is_corresponding":false},{"id":255746,"name":"Peter S. Nelson","orcid":"0000-0002-5451-5726","position":7,"is_corresponding":false},{"id":255747,"name":"Bruce Montgomery","orcid":"0000-0003-4459-0295","position":8,"is_corresponding":false},{"id":255745,"name":"Evan Y. Yu","orcid":"0000-0002-1510-8044","position":9,"is_corresponding":false},{"id":255742,"name":"Michael T. Schweizer","orcid":"0000-0002-5510-0661","position":10,"is_corresponding":false},{"id":448834,"name":"Alexander Carlson","orcid":"0000-0002-4020-5233","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:01:22.387926Z","pmid":"32997692","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}