HER2 Alteration Testing In Advanced and Metastatic NSCLC

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HER2 mutations in non–small cell lung cancer (NSCLC) represent a critical actionable driver alteration that requires comprehensive next-generation sequencing testing for all stage IV patients.Isabel Preeshagul, DO, MBS,emphasizes that full-panel DNA-based testing is essential to identify HER2 alterations, also known as ERBB2 mutations, which encode for cell surface receptors. This upfront testing approach ensures oncologists don't miss any treatable driver mutations in patients with advanced lung cancer.

The distinction between HER2 mutation, amplification, and overexpression is crucial for treatment selection in NSCLC. Unlike breast cancer where HER2 overexpression is commonly assessed through immunohistochemistry, lung cancer requires specific focus on HER2 exon 20 mutations detected through next-generation sequencing. HER2 amplification involves multiple gene copies, while HER2 mutation represents actual genetic alterations in the ERBB2 gene. Both types of alterations can occur simultaneously or independently, making comprehensive testing protocols essential.

Modern biomarker testing strategies for HER2-mutated NSCLC patients should include both DNA sequencing for mutations and copy number analysis for amplification. This dual approach maximizes the identification of patients who may benefit from HER2-targeted therapies. The testing methodology directly impacts treatment options, as different HER2 alterations respond to different therapeutic approaches, highlighting the importance of precise molecular characterization in personalized lung cancer care.