CDK4 and breast cancer: Palbociclib is a selective CDK4/6 inhibitor and has been approved for treating patients with ER-positive, HER2-negative advanced breast cancer.4 Palbociclib inhibits the activity of the CDK4/6-cyclin D1 complex, resulting in reduced phosphorylation of retinoblastoma (Rb) protein which in turn attenuates the release of E2F transcription factors from the pRb-E2F complex, thereby leading to the G0/G1 phase arrest and block of S-phase entry.5