Croessman et al. found that the HER2 L755S mutation promotes HER2-HER3 heterodimerization, leading to PI3K/AKT/mTOR axis hyperactivation and estrogen resistance in ER+ breast cancer, indicating that dual blockade of the HER2 and ER pathways is required for the treatment of ER+/HER2-mutated breast cancer [29]. The gene discussed is ERBB2; the disease is breast cancer.