Clinical Implications of BRCA Mutations in Advanced Biliary Tract Cancer
- 18 October 2022
- journal article
- research article
- Published by S. Karger AG in Oncology
- Vol. 101 (1), 41-48
- https://doi.org/10.1159/000527525
Abstract
Introduction: 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.Keywords
This publication has 26 references indexed in Scilit:
- Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective StudyThe Oncologist, 2017
- Update on the Diagnosis and Treatment of CholangiocarcinomaCurrent Gastroenterology Reports, 2017
- Molecular profiling of biliary tract cancer: a target rich diseaseJournal of Gastrointestinal Oncology, 2016
- BRCAness revisitedNature Reviews Cancer, 2016
- Genomic spectra of biliary tract cancerNature Genetics, 2015
- CholangiocarcinomaThe Lancet, 2014
- New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation SequencingThe Oncologist, 2014
- Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract CancerThe New England Journal of Medicine, 2010
- Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategyNature, 2005
- Improved survival in women with BRCA‐associated ovarian carcinomaCancer, 2003