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Article / Publication Details AbstractIntroduction: Current standard chemotherapy for biliary tract cancer (BTC) has limited survival benefits, and the need for targeted therapies is increasing. This study investigated the genetic profiles and clinical implications of BRCA mutations in patients with advanced BTC. Methods: Targeted high-throughput sequencing was performed on samples obtained from 25 patients with advanced BTC who had received palliative first-line platinum-based chemotherapy. Results: Of the 25 patients, 16 (64.0%) were younger than 65 years of age and 16 (64.0%) were male. The BTC cases consisted of intrahepatic cholangiocarcinoma (9, 36.0%), extrahepatic cholangiocarcinoma (5, 20.0%), and gallbladder cancer (11, 44.0%). The median overall survival (OS) and progression-free survival (PFS) of all patients were 11.9 months (95% confidence interval [CI] 9.233–14.567) and 5.6 months (95% CI 3.812–7.321), respectively. Genomic alterations in TP53 (52.0%), BRCA (36.0%), ATM (32.0%), ERBB2 (24.0%), NOTCH1 (20.0%), and FGFR3 (20.0%) were frequently reported. TP53 and ATM mutations were associated with OS (TP53: hazard ratio [HR] 2.719, 95% CI 1.074–6.881, p = 0.035; ATM: HR 2.780, 95% CI 1.091–7.082, p = 0.032). Patients with BRCA mutations had a slightly improved PFS compared to those with intact BRCA (6.7 months [range, 2.674–10.660 months] vs. 5.3 months [range, 3.601–6.999 months], p = 0.090). However, there was no significant difference in OS between groups (BRCA mutant vs. intact: 10.6 months [range, 3.588–17.612 months] vs. 11.9 months [range, 7.499–16.301 months], p = 0.252). BRCA mutations were significantly associated with PFS in the multivariate analysis (HR 0.150, 95% CI 0.034–0.655, p = 0.012). Conclusion: This study demonstrated that BRCA mutations might have a role as predictive biomarkers for palliative first-line platinum-based chemotherapy in patients with advanced BTC.
S. Karger AG, Basel
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