This study aims to lay the groundwork for future targeted therapies by presenting proteomic and genomic evidence that ZMIZ1 is co-expressed with ER in patient tumours and that the inhibition in ZMIZ1 reduces the early transcriptional response of cell cycle genes to estrogen in ER-positive breast cancer cells via a novel ZMIZ1–ER–E2F2 signalling axis. Here, ESR1 is linked to breast cancer.