Real‐World Landscape of BRCA Deleterious Alterations in Advanced Prostate Cancer: Insights From a Nationwide Genomic Database
Hideyasu Tsumura, Dai Koguchi, Ken‐ichi Tabata, Izuru Shiba, Shuhei Hirano, Masaomi Ikeda, Takefumi Satoh, Keiko Takahashi, Naomi Araki, Akinori Watanabe, Tsutomu Yoshida, Jiichiro Sasaki, Fumio Takada, Kazumasa MatsumotoABSTRACT
Background
The clinical characteristics of BRCA1 and BRCA2 ( BRCA ) deleterious alterations in advanced prostate cancer—considering age, family history, co‐occurring gene alterations, and variant type—remain incompletely understood in patients undergoing tumor‐only panel testing.
Materials and Methods
We analyzed 2,815 patients who underwent comprehensive cancer genomic profiling (CGP) using a tissue‐based tumor‐only panel from December 2020 to November 2024. Eligible patients had metastatic prostate cancer resistant to standard therapies or androgen‐indifferent prostate cancer, including neuroendocrine prostate cancer. Data were obtained from the Center for Cancer Genomics and Advanced Therapeutics, a nationwide CGP database in Japan.
Results
Median age at CGP testing was 72 years (range 23–93 years). BRCA deleterious alterations were detected in 428 patients (15.2%), decreasing with age: 24.2% (< 50 years), 25.4% (50–59 years), 16.3% (60–69 years), 14.3% (70–79 years), and 9.3% (≥ 80 years). A family history of breast or ovarian cancer independently predicted BRCA alterations (odds ratio 1.901 and 3.016; both p < 0.05). RB1 alterations and MYC amplification were significantly enriched as co‐occurring alterations in BRCA2 (6.9% vs. 14.9%, 15.4% vs. 23.1%; both p < 0.05). Stratified by BRCA2 variant type, patients with homozygous deletion (HD) had longer overall survival than those with truncating alterations following olaparib treatment (median 30.6 vs. 16.9 months; hazard ratio 0.373; 95% CI 0.220–0.633).
Conclusions
In advanced, therapy‐resistant prostate cancer, BRCA deleterious alterations were more frequent in younger patients and those in with a family history of breast and ovarian cancer. BRCA2 HD was significantly associated with a favorable response to olaparib.