CDK4 and breast cancer: Since the late 1970s, endocrine therapy regimens, such as anastrozole, exemestane, fulvestrant, goserelin, letrozole, tamoxifen, and toremifene, have been investigated for the treatment of HR-positive breast cancers.22,23,24,25,26,27,28 In more recent years, targeted therapies such as palbociclib, ribociclib, and abemaciclib, which target the cyclin-D–CDK4/6–Rb pathway, have been tested.