Concurrently, MDM2—overexpressed in 20%–30% of breast cancers—antagonizes p53-mediated cell cycle arrest by degrading p53 and suppressing its activation of p21 CIP1, thereby bypassing CDK4/6 inhibitor-induced G1 arrest (Efeyan et al., 2007; Portman et al., 2021). This evidence concerns the gene CDK4 and breast cancer.