Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort
In 260 gallbladder cancer patients from New York and Santiago, HER2 gene changes were found in about one in seven at both centres, split between extra copies and point mutations, and patients with them lived longer.
Overview
260 patients with gallbladder cancer, 237 from Memorial Sloan Kettering and 23 from the Pontificia Universidad Catolica de Chile, were profiled with MSK-IMPACT. Clinical characteristics did not differ except gallstone prevalence, which was higher in Chile (85% versus 44%; P = 0.0003). The prevalence of ERBB2 alterations was comparable (15% versus 9%; P = 0.42).
Overall, ERBB2 alterations were present in 14% of patients: 8% amplification, 4% mutation, 1.5% concurrent amplification and mutation, and 0.4% fusion. Patients whose tumours harboured ERBB2 alterations had better overall survival than ERBB2 wild-type patients (22.3 versus 11.8 months; P = 0.024).
- ERBB2 altered in 14% overall: 8% amplification, 4% mutation, 1.5% both, 0.4% fusion.
- 15% (United States) versus 9% (Chile), not significantly different; gallstones 44% versus 85%.
- Overall survival 22.3 versus 11.8 months with and without an ERBB2 alteration (P = 0.024).
The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.
- Only 23 Chilean patients.
- Survival advantage may reflect access to HER2-directed therapy at MSK rather than biology.
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