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. 2025 Sep;10(9):105563.
doi: 10.1016/j.esmoop.2025.105563. Epub 2025 Sep 5.

HER2DX ERBB2 score in advanced HER2-positive gastric cancer treated with trastuzumab and chemotherapy

D Pesántez  1 , F Brasó-Maristany  2 , T Pascual  3 , L Angelats  4 , A Indacochea  4 , M Cuatrecasas  5 , S López  6 , E Sanfeliu  7 , G Fernández-Esparrach  8 , L Notario  9 , I Méndez  10 , D Momblan  11 , L Candia  4 , I Macias  4 , A Prat  12 , T Sauri  3
Affiliations

HER2DX ERBB2 score in advanced HER2-positive gastric cancer treated with trastuzumab and chemotherapy

D Pesántez et al. ESMO Open. 2025 Sep.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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).

Conclusions: 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.

Keywords: ERBB2; HER2-positive; HER2DX; gastric cancer; genomics.

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Figures

Figure 1
Figure 1
ERBB2 messenger RNA (mRNA) expression in advanced gastric cancer. (A) ERBB2 mRNA expression assessed at the nCounter platform across the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) subgroups. P values were determined using one-way analysis of variance. (B) Representative images of the different levels of HER2 analyzed by IHC and in situ hybridization (ISH).
Figure 2
Figure 2
HER2DX ERBB2 score in 58 patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) treated with trastuzumab combined with chemotherapy (T-chemo). (A) Distribution of HER2DX ERBB2 score groups according to the predefined cut-offs in breast cancer. (B) Distribution of HER2DX ERBB2 score groups across HER2 IHC classification. ISH, in situ hybridization.
Figure 3
Figure 3
Association of HER2DX ERBB2 score groups with survival outcome. (A) Progression-free survival (PFS). (B) Overall survival (OS). CI, confidence interval; HR, hazard ratio; Ref. reference.
See this image and copyright information in PMC

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