Clinical and Genomic Characterization of <i>ERBB2</i>-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort.

Abstract

Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on <i>ERBB2</i> alterations. Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets. A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% <i>v</i> 44%; <i>P</i> = .0003). The prevalence of <i>ERBB2</i> alterations was comparable between the two cohorts (15% <i>v</i> 9%; <i>P</i> = .42). Overall, <i>ERBB2</i> alterations were present in 14% of patients (8% with <i>ERBB2</i> amplification, 4% <i>ERBB2</i> mutation, 1.5% concurrent amplification and mutation, and 0.4% <i>ERBB2</i> fusion). Notably, patients with GBC that harbored <i>ERBB2</i> alterations had better overall survival (OS) versus their <i>ERBB2</i>-wild type counterparts (22.3 months <i>v</i> 11.8 months; <i>P</i> = .024). The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of <i>ERBB2</i> alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.