Real-World Landscape of Genomic Medicine in Breast Cancer Revealed by the C-CAT Database: Reappraisal of Drug Accessibility and Clinical Utility in 6,307 Patients

Background Comprehensive genomic profiling (CGP) has advanced precision oncology in breast cancer, yet its real-world contribution to treatment selection in Japan remains unclear. Methods We analyzed 6,307 Japanese patients with breast cancer who underwent CGP in the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. Drug accessibility to Pharmaceuticals and Medical Devices Agency (PMDA)-approved therapies was assessed using two criteria, excluding biomarkers identifiable by prior companion diagnostics: Criterion I reflecting phase III breast cancer trials, and Criterion II reflecting phase I/II basket or tumor-agnostic trials. Evidence levels at testing were compared with those reassessed using evidence available as of October 2025. Results At least one genomic alteration was detected in 97.6% of cases; TP53 (53.9%), PIK3CA (37.7%) were most frequent. Re-evaluation increased Evidence Level A assignments from 3,757 to 5,874. Nevertheless, biomarkers linked to PMDA-approved therapies were limited to ten categories: PIK3CA/AKT1/PTEN alterations, ERBB2 amplification, BRCA1/2 mutations, NTRK fusions, BRAF V600 mutation, and TMB-H/MSI-H. Drug accessibility was 30.8% under Criterion I, driven exclusively by eligibility for capivasertib. Under Criterion II, the accessibility was 19.5%, comprising ERBB2 amplification (4.7%), somatic BRCA1/2 mutations (3.4%), NTRK fusions (0.1%), BRAF V600 mutation (0.2%), and non-overlapping TMB-H/MSI-H (11.1%). The prevalence of somatic BRCA1/2 mutations in germline BRCA1/2 noncarriers were identified in 3.4%, representing the first large-scale estimate in Japanese breast cancer. Conclusion Despite high detection rates, translation into PMDA-approved therapies remains limited, underscoring the need to optimize testing timing, expand trial access, harmonize molecular tumor boards practice, and consider breast cancer–specific mini-panels.