In particular, cyclin D bind to CDK4 and CDK6, induce hyperphosphorylation of retinoblastoma protein (Rb), promote E2F-mediated cell cycle gene transcription, and promotes tumor cell progression from the G1 to S phase of the cell cycle, which promotes breast cancer cell proliferation a pathway closely associated with ET resistance in patients with HR+ breast cancer (Roberto et al. 2021; Lloyd et al. 2022; Alves et al. 2021). This evidence concerns the gene CDK4 and breast cancer.