Collectively, our results suggest that although ER has been shown to be a negative regulator of p53 [14, 45, 46], it is the anti-proliferative actions of fulvestrant (particularly where they overlap with CDK4/6 inhibition) and MDM2 inhibition interacting via cell cycle progression pathways that combine to produce an enhanced anti-tumour effect. Here, CDK4 is linked to neoplasm.