CDK4 and breast tumor luminal A or B: CDK4/6 inhibitors in SHR-positive breast cancer: Due to the central role of Cyclin D/CDK4/6 complex in the control of the breast cancer proliferation and in the estrogen receptor signaling pathway, several CDK4/6 inhibitors have been investigated as breast cancer therapeutics in the last decades, in particular in luminal breast cancer (Figure 4).