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. Here, PREX1 is linked to breast cancer.