In this study, we finely map the heterogeneity of response to estrogen across time using single-cell RNA sequencing (scRNA-seq) and single-cell multiome (joint ATAC-RNA profiling) in multiple ER positive (ER+) breast cancer cell lines and patient-derived explant organoid (PdXO) models with the aim of identifying regulatory mechanisms driving heterogeneous hormone response rates. Here, ESR1 is linked to breast carcinoma.