Three CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have been approved for the first-line therapy of patients with HR-positive and HER2-negative breast cancers in combination with nonsteroidal aromatase inhibitors [176–179] or SERD (fulvestrant) [180, 181] (Fig. 3g), thereby delaying or overcoming endocrine resistance [182]. This evidence concerns the gene ERBB2 and breast cancer.