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Human epidermal growth factor 2/NEU (HER2) aberrations account for 4.7–10% of all non-small cell lung cancers (NSCLC), making it one of the more prevalent forms of NSCLC. Human epidermal growth factor 2 aberrations also instigate breast cancer and these patients commonly demonstrate a robust response to HER targeted immunotherapies. This optimistically promised that HER2 NSCLC might also respond via the same pathophysiologic mechanisms. To date, this promise has largely failed to deliver, and an early trial ended in cancellation due to lack of efficacy. Contrary to this lack of efficacy, this case presents a patient with HER2 positive NSCLC with a specific gene amplification that demonstrated response to HER2 therapy. This adds to the growing evidence that targeted therapy can be efficacious in some HER2 positive NSCLC. It further reinforces the need for extended mutational testing in lung cancer patients, particularly those with a smoking history.

Human epidermal growth factor 2 (HER2) non-small cell lung cancer (NSCLC) with YVMA mutation responsive to ado-trastuzumab emtansine