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<p>We present a case of advanced gastroesophageal junction adenocarcinoma initially diagnosed as Human epidermal growth factor receptor 2 (HER2)-negative based on immunohistochemistry (IHC) of a metastatic lymph node biopsy. The patient developed progressive disease despite multiple lines of systemic chemotherapy. Comprehensive genomic profiling (CGP) performed on archived primary tumor tissue revealed high-level <i>ERBB2</i> amplification. Reassessment of HER2 status using IHC on the primary tumor confirmed strong HER2 overexpression (IHC 3+). Based on this finding, the patient was treated with trastuzumab plus FOLFOX followed by trastuzumab deruxtecan (T-DXd), achieving a durable response. Notably, the esophageal stricture caused by cervical lymphadenopathy resolved completely, and the patient remained progression-free for over 21 months with T-DXd therapy. This case highlights the clinical significance of intratumoral HER2 heterogeneity and underscores the importance of reassessing biomarkers in patients with refractory disease. It also illustrates the potential role of CGP in identifying overlooked therapeutic targets and guiding subsequent treatment decisions in gastric cancer. CGP may serve as a useful adjunct to conventional diagnostics, particularly when initial testing is inconclusive or based on metastatic tissue.</p>

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HER2 reassessment triggered by comprehensive genomic profiling reveals a therapeutic opportunity in refractory gastric cancer: a case report

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Takaaki Iwado,
  • Yoshiyasu Kono,
  • Motoyuki Otsuka

摘要

We present a case of advanced gastroesophageal junction adenocarcinoma initially diagnosed as Human epidermal growth factor receptor 2 (HER2)-negative based on immunohistochemistry (IHC) of a metastatic lymph node biopsy. The patient developed progressive disease despite multiple lines of systemic chemotherapy. Comprehensive genomic profiling (CGP) performed on archived primary tumor tissue revealed high-level ERBB2 amplification. Reassessment of HER2 status using IHC on the primary tumor confirmed strong HER2 overexpression (IHC 3+). Based on this finding, the patient was treated with trastuzumab plus FOLFOX followed by trastuzumab deruxtecan (T-DXd), achieving a durable response. Notably, the esophageal stricture caused by cervical lymphadenopathy resolved completely, and the patient remained progression-free for over 21 months with T-DXd therapy. This case highlights the clinical significance of intratumoral HER2 heterogeneity and underscores the importance of reassessing biomarkers in patients with refractory disease. It also illustrates the potential role of CGP in identifying overlooked therapeutic targets and guiding subsequent treatment decisions in gastric cancer. CGP may serve as a useful adjunct to conventional diagnostics, particularly when initial testing is inconclusive or based on metastatic tissue.