NR1H4 and breast neoplasm: FXR activation mediates ER activation and promotes cell proliferation, but this effect is lost when estrogen is inhibited.195 In a follow-up analysis of 81 patients with distant breast metastases, this team confirmed a strong correlation between FXR expression in primary breast tumors and the development of bone metastases.196 The results of this series of studies suggest that the use of FXR agonists in cancer patients may promote tumor growth and bone metastasis.