How do you differentiate between ERBB2 mutation vs HER2 overexpression testing when selecting patients for tumor-agnostic therapy?  

In my practice, I recommend next-generation sequencing to assess for actionable genomic alterations, as well as HER2 IHC, for patients with advanced/metastatic cancer.

This distinction is critical. HER2 protein overexpression (IHC ± ISH) underpins T-DXd’s tumor-agnostic approval. ERBB2 mutations define a different subset that perhaps may have better responses to HER2 TKIs that are in development rather than ADCs. In other words, a genomic alteration i...