Due to reports of antagonistic crosstalk between E2 and Smad-mediated TGFβ signaling in breast cancer cells [34,35,37,38,39,40] and our previous demonstration of the E2-dependency of osteolysis in ER+ MCF-7 BMETs [12], the time dependent effects of each agent on expression and/or activation of the opposing receptor were assessed in bone-tropic ER+ tumor cells. The gene discussed is ESR1; the disease is breast carcinoma.