We show pathways associated with endocrine resistance can be further upregulated in RB competent yet CDK4/6 resistant cell lines suggesting that some tumours may remain hardwired to the RB/E2F transcriptional axis and use flexibility in kinase signalling to circumvent the G1/S checkpoint by increasing expression of CCNE1 leading to hyperphosphorylation of RB and reducing dependence on ER signalling as a mitogenic driver. This evidence concerns the gene RB1 and neoplasm.