In conclusion, while the study of ER+ breast cancer BMETs is complicated by the duality of ERα signaling effects in bone vs. bone-disseminated ER+ tumor cells, the experiments reported here, by taking advantage of differential dose-dependent effects of E2 on bone vs. ER+ tumor-associated osteolysis, suggest that ER+ osteolytic BMET progression may be specifically promoted by tumoral ERα signaling via the induction of osteolysis. The gene discussed is ESR1; the disease is neoplasm.