Genomic landscape and clinical impact of BRCA1/2 pathogenic variants in metastatic castration-resist
Poly (ADP-ribose) polymerase (PARP) inhibitors provide clinical benefit for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 pathogenic variants. This study aimed to investigate the genomic landscape of mCRPC and evaluate the prognostic and therapeutic impact of pathogenic BRCA1/2 variants. We conducted a retrospective cohort study of 5893 patients with mCRPC registered in Japan. Overall survival (OS) was compared according to homologous recombination repair (HRR) gene alteration status and specific BRCA1/2 pathogenic variants. Of 5893 patients, 2203 carried at least one pathogenic variant in HRR genes, and 792 had BRCA1/2 pathogenic variants. Olaparib was recommended for all patients with BRCA1/2 pathogenic variants, of whom 389 received the treatment. Patients with HRR gene alterations had significantly shorter OS than those without (P = 0.023). Among olaparib-treated patients, BRCA1 pathogenic variants were significantly associated with worse O
Nature
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