These molecular findings triggered interest in CDK4/6 inhibitors for breast cancer treatment, culminating in several recently published large phase III clinical trials (PALOMA-2/3, MONALEESA-2, and MONARCH-2) that tested addition of different CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib, respectively) to hormonal therapies in ER-positive HER2-negative MBC (75, 97, 140, 141). Here, ESR1 is linked to breast carcinoma.