This is a relevant question since in vitro evidence in ER+ human breast cancer cells of reciprocal expression of ERα and TGFβRII [34,35,36] and E2 inhibition of TGFβ-induced Smad signaling [37,38,39,40] suggests that anti-TGFβ therapeutics could be less effective for the majority of patients with BMETs, i.e., those with ER+ tumors, if tumoral TGFβ signaling in ER+ cells does not contribute to osteolytic BMET progression. The gene discussed is ESR1; the disease is breast carcinoma.