Distinguishing HER2 Mutation From Amplification and Overexpression in NSCLC

This episode opens with a distinction that matters more in lung cancer than many oncologists expect. The panel separates HER2 protein overexpression, gene amplification, and activating mutation, explaining why the mutation behaves as a true oncogenic driver rather than a descriptive marker of tumor biology, and why the familiar breast and gastric cancer frameworks do not transfer cleanly to non–small cell lung cancer. The discussion turns to how clinicians explain that difference to patients, framing immunohistochemistry as a look at protein expression and next-generation sequencing as a look at the DNA itself, and why a DNA-level finding more reliably predicts response to targeted therapy. Attention then moves to testing strategy in community practice, including the persistent confusion between immunohistochemistry and sequencing, the risk that narrow or single-gene panels miss ERBB2 exon 20 insertions entirely, and payer restrictions that push practices toward less comprehensive testing than the current treatment landscape requires.