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Background <p>Gastric adenocarcinoma remains a significant cause of cancer-related mortality globally. Human epidermal growth factor receptor 2 (HER2) overexpression is identified in a proportion of gastric and gastroesophageal junction adenocarcinomas. Although HER2-targeted therapy is well established in metastatic disease, its role in the neoadjuvant setting is not clearly defined.</p> Methods <p>In this prospective observational study, 43 patients with resectable gastric or gastroesophageal junction adenocarcinoma (cT2–T4 and/or cN+) were included. All patients received standard neoadjuvant chemotherapy (FLOT, XELOX, or FOLFOX) followed by curative gastrectomy with D2 lymphadenectomy. Pathological response was evaluated using the Becker tumor regression grading (TRG) system. HER2 status was assessed by immunohistochemistry, with fluorescence in situ hybridization performed for equivocal (IHC 2+) cases. The relationship between HER2 expression and pathological response was analyzed.</p> Results <p>HER2 overexpression was detected in 10 of 43 patients (23.25%). A favorable pathological response (TRG 1–2) occurred significantly less often in HER2-positive tumors compared with HER2-negative tumors (30.0% vs. 84.8%; <i>p</i> = 0.002). In contrast, an unfavorable response (TRG 3) was significantly more frequent among HER2-positive cases (70.0% vs. 15.2%; <i>p</i> = 0.002).</p> Conclusion <p>HER2 overexpression is associated with poorer pathological response to standard neoadjuvant chemotherapy in gastric adenocarcinoma. These findings highlight the potential need for molecularly tailored perioperative treatment strategies in this subgroup.</p>

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Response of Gastric Adenocarcinoma to Neoadjuvant Chemotherapy in Relation to HER2 Overexpression: a Prospective Observational Study

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Pratap Kumar Deb,
  • Samir Bhattacharyya,
  • Subrata Kumar Sahu,
  • Arnab Gupta

摘要

Background

Gastric adenocarcinoma remains a significant cause of cancer-related mortality globally. Human epidermal growth factor receptor 2 (HER2) overexpression is identified in a proportion of gastric and gastroesophageal junction adenocarcinomas. Although HER2-targeted therapy is well established in metastatic disease, its role in the neoadjuvant setting is not clearly defined.

Methods

In this prospective observational study, 43 patients with resectable gastric or gastroesophageal junction adenocarcinoma (cT2–T4 and/or cN+) were included. All patients received standard neoadjuvant chemotherapy (FLOT, XELOX, or FOLFOX) followed by curative gastrectomy with D2 lymphadenectomy. Pathological response was evaluated using the Becker tumor regression grading (TRG) system. HER2 status was assessed by immunohistochemistry, with fluorescence in situ hybridization performed for equivocal (IHC 2+) cases. The relationship between HER2 expression and pathological response was analyzed.

Results

HER2 overexpression was detected in 10 of 43 patients (23.25%). A favorable pathological response (TRG 1–2) occurred significantly less often in HER2-positive tumors compared with HER2-negative tumors (30.0% vs. 84.8%; p = 0.002). In contrast, an unfavorable response (TRG 3) was significantly more frequent among HER2-positive cases (70.0% vs. 15.2%; p = 0.002).

Conclusion

HER2 overexpression is associated with poorer pathological response to standard neoadjuvant chemotherapy in gastric adenocarcinoma. These findings highlight the potential need for molecularly tailored perioperative treatment strategies in this subgroup.