Based on pathologic HER2 classification, ~40%-60% of patients with breast cancer could meet the current criteria for HER2 low status, out of which nearly 80% are HR+ and 20% are HR negative.68-70 The DESTINY-Breast 04 trial demonstrated that patients with previously treated, metastatic HER2 low breast cancer had an improved PFS (9.9 vs. 5.1 months, P < .001) and OS (23.4 vs. 16.8 months, P = .001) with T-DXd compared to physician’s choice of chemotherapy.71 This represents a paradigm shift for this group of patients, who were otherwise ineligible for HER2-directed therapies. The gene discussed is ERBB2; the disease is breast cancer.