By using genetic, cellular, and molecularapproaches, we found that RUNX1 is a key regulator of estrogen receptor (ER)-positivemature ductal luminal cells, and that the loss of RUNX1 may contributeto the development of ER+ luminal breast cancer when under thebackground of either TP53 or RB1 loss. Here, RUNX1 is linked to breast carcinoma.