The retinoblastoma protein (Rb) is a tumour suppressor best known for repressing E2F transcription factors and halting cell cycle progression. In hormone receptor-positive (HR+) breast cancer, CDK4/6 inhibitors activate Rb by preventing its phosphorylation, forming a key component of current endocrine therapy regimens. How pharmacologically activated Rb remodels chromatin and influences transcriptional networks beyond cell cycle arrest remains poorly understood. Here we show that CDK4/6 inhibition induces widespread redistribution of hypo-phosphorylated Rb to both promoters and enhancers in cancer cells. While Rb predictably binds to cell cycle gene promoters to repress transcription, at other sites it unexpectedly promotes expression of oestrogen-responsive genes by integrating into oestrogen receptor (ER)-rich transcriptional hubs. CDK4/6 inhibition enhances ER target gene expression in breast cancer cells, patient-derived xenografts, and clinical samples of HR+ breast cancer – a phenomenon that is Rb-dependent. This transcriptional reprogramming is mediated in part by KDM5A, whose functional interaction with Rb contributes to gene regulation at these oestrogen-responsive loci. Critically, components of this Rb-driven ER transcriptional program are pro-proliferative. In endocrine-sensitive tumours, this can be therapeutically neutralised with concomitant anti-oestrogen therapy, explaining potent therapeutic synergy. In endocrine-resistant contexts – such as ESR1-mutant breast cancer – the Rb-driven oestrogenic programme persists, serving to limit therapeutic efficacy. These findings reframe Rb as a dual-function transcriptional regulator: while enforcing cell cycle arrest, it can also activate lineage programs that counteract its own tumour suppressor function to shape therapeutic outcomes.