Multi-institutional retrospective analysis of HER2 positivity as prognostic biomarker and therapeutic target in advanced biliary tract cancer

A retrospective analysis of patients from Yonsei University (Seoul, South Korea) and MD Anderson Cancer Center (Houston, TX) evaluated the prognostic relevance of HER2 positivity and the clinical impact of anti-HER2 therapy in the management of advanced biliary tract cancer (aBTC). The analysis included 388 patients with aBTC and known HER2 status between 2009 and 2023. HER2 positivity was defined as HER2 IHC 3+, IHC 2+ with in situ hybridization positivity, or ERBB2 amplification. HER2 positivity, observed in 25.2%, was associated with shorter overall survival (median 13.7 versus 17.1 months; HR 1.25; 95% CI 0.97-1.60) and significantly shorter first-line progression-free survival (median 5.1 versus 7.4 months; HR 1.91; 95% CI 1.46-2.48) compared with HER2 negativity. Anti-HER2 therapy significantly improved OS among HER2-positive patients (median 18.2 versus 8.1 months; HR 0.39; 95% CI 0.21-0.62). The authors conclude that HER2 is a clinically meaningful biomarker with prognostic and predictive relevance in aBTC.