Response to trastuzumab combined with chemotherapy (T-chemo) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) varies widely, highlighting the need for more precise biomarkers beyond conventional HER2 assessment with immunohistochemistry (IHC) and in situ hybridization (ISH). The HER2DX ERBB2 messenger RNA (mRNA) assay, a clinically validated genomic test initially developed for early-stage HER2-positive breast cancer, quantitatively measures ERBB2 expression and may improve patient selection for T-chemo in AGC. In a retrospective cohort of 134 patients with AGC, including 58 who received T-chemo, we evaluated whether the HER2DX ERBB2 score defines more accurately HER2 status and correlates with treatment response and survival outcomes in HER2-positive AGC, compared with standard pathology-based methods. Our findings demonstrate that a high HER2DX ERBB2 score was significantly associated with improved progression-free survival hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.95, P = 0.012 and overall survival (HR 0.43, 95% CI 0.23-0.81, P = 0.008). These results suggest that ERBB2 mRNA expression, as measured by HER2DX, may help refine selection for T-chemo and guide more personalized treatment strategies in HER2-positive AGC.
Pesántez et al. (2025) studied this question.