Dysregulation of the cyclin D–CDK4/6 inhibitor of CDK4 (INK4)–retinoblastoma (Rb) pathway in breast cancer cells has been associated with endocrine therapy resistance [18], and preclinical studies in HR+ breast cancer models have demonstrated improved efficacy when CDK4/6 inhibitors are combined with endocrine therapy [19–22]. This evidence concerns the gene RB1 and breast cancer.