Mutations in RB1, a tumor suppressor regulating the G1-S phase transition through transcriptional repression of E2F1 [159], are frequently found in patients treated with CDK4/6 inhibitors [160], which in combination with an aromatase inhibitor, have become the preferred frontline therapy for endocrine-sensitive metastatic HR+/HER2− breast cancer [161]. Here, CDK4 is linked to breast carcinoma.