Accordingly, M/D-driven tumors emerged with delayed kinetics in mice bearing a deletion in Esr1 causing defective transcriptional activity (ER-AF20)13 (Fig. 1e), while oncogenesis and tumor progression were accelerated in mice expressing an ER mutant associated with increased nuclear accumulation (ERC451A)14 (Fig. 1f). Here, ESR1 is linked to neoplasm.