However, the need for HER2 amplification or mutation to achieve T-DXd clinical benefit has been questioned based on the compelling clinical activity of T-DXd in patients with HER2-low (IHC 1+ or 2 + /ISH-negative)18 and even HER2 “ultra-low” (IHC 0 with membrane staining)20 breast cancers. The gene discussed is ERBB2; the disease is breast cancer.