CDK4 and breast cancer: There are currently three CDK4/6i that have been approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for metastatic endocrine-receptor (ER)-positive and HER-2 negative breast cancer in combination with aromatase inhibitors (AI) or fulvestrant, namely: abemaciclib, palbociclib, and ribociclib.