CDK4 and breast cancer: Recently, selective CDK4/6 inhibitors have shown impressive results when combined with endocrine therapies (e.g., letrozole and fulvestrant) in advanced breast cancer, leading to the FDA approval of three compounds: palbociclib, ribociclib and, most recently, abemaciclib.35,36 Of note, the antimetastatic activity that is triggered by CDK4/6 inhibition can be regulated independently from primary tumor development.37 However, the underlying mechanisms are not clearly understood.