ABSTRACT Aim This systematic review and meta‐analysis aimed to clarify the prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression on overall survival (OS) and progression‐free survival (PFS) in advanced and resectable gastric cancer. Methods We systematically searched electronic databases for studies reporting survival outcomes associated with HER2 overexpression in gastric cancer patients. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were pooled using random‐effects models. Results A total of 39 studies with 19 903 gastric cancer patients were included. The pooled rate of HER2 overexpression was estimated at 16% (95% CI, 14% to 18%). Our analysis revealed that HER2 overexpression was significantly associated with worse OS (HR = 1.30, 95% CI 1.12 to 1.51; p < 0.01) and PFS (HR = 1.57, 95% CI: 1.09 to 2.26; p < 0.01). The association with worse OS was significant across the studies with resectable (HR = 1.31, 95% CI: 1.08 to 1.60; p < 0.01) and advanced (HR = 1.25, 95% CI: 1.00 to 1.58; p = 0.04) gastric cancer patients. However, the association between HER2 and PFS was only significant in the resectable subgroups (HR = 2.28, 95% CI: 1.09 to 4.74; p < 0.01), not in the advanced subgroup (HR = 1.18, 95% CI: 0.93 to 1.51; p = 0.16). Conclusions HER2 overexpression appears to be associated with poorer outcomes in advanced and resectable gastric cancer. Standardizing diagnostic criteria and integrating HER2 assessment into multimarker panels could enhance prognostic accuracy and guide personalized therapeutic decisions.
Pourfaraji et al. (Mon,) studied this question.