To address these knowledge gaps regarding the effects of ERα signaling in the tumor itself vs. the bone microenvironment in driving tumor-associated osteolysis and osteolytic progression for ER+ BMET, E2 effects were assessed in a murine model of osteolytic ER+ BMET using intracardiac (IC) injection of ER+ human breast cancer cells. Here, ESR1 is linked to breast carcinoma.