Despite the well-characterized function of tumoral TGFβ signaling in driving the “vicious cycle of osteolysis” demonstrated in preclinical models of ER- breast cancer BMETs, little is known about the role of tumoral TGFβ signaling in ER+ BMETs, a subtype that comprises over 70% of breast cancer BMETs [5,6,7,8]. The gene discussed is ESR1; the disease is breast carcinoma.