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HER2 Loss Gastric — SCE Medical Oncology MCQ

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ModerateGI CancersHER2 Loss GastricSCE Medical Oncology

A 70-year-old man with metastatic gastric cancer is started on trastuzumab for HER2-positive disease. After 6 months, repeat biopsy of a progressing site shows loss of HER2 amplification (now IHC 1+). What is this phenomenon called?

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Correct answer: B — HER2 temporal heterogeneity/loss — tumour evolution under anti-HER2 selective pressure can result in loss of HER2 expression, rendering continued anti-HER2 therapy ineffective

HER2 expression can change during treatment (temporal heterogeneity), with loss of HER2 amplification occurring in approximately 30-40% of gastric cancers during trastuzumab therapy. This represents tumour evolution under selective therapeutic pressure (HER2-negative clones outgrow HER2-positive clones). Re-biopsy at progression is recommended in gastric cancer to reassess HER2 status and guide subsequent therapy. This is a key reason why serial molecular profiling is important in gastric cancer.

Reference: ESMO 2024 Gastric Cancer Guidelines; Pietrantonio et al Ann Oncol 2016