ESR1 and breast cancer: Thus, while prior experiments utilizing E2-driven ER+ human breast cancer xenograft models and a single dose of E2 have demonstrated tamoxifen-inhibition of ER+ BMET following intracardiac tumor cell inoculation, or a role of zoledronic acid or tumor cell PREX1 expression in regulating dissemination of ER+ cells from primary orthotopic tumors ultimately home to bone[18,21,27], none have been able to elucidate the relative importance of bone vs. tumor effects of E2, or other agents with dual bone vs. tumor effects, such as zoledronic acid.