ESR1 and breast carcinoma: Although tamoxifen is an ER blocker and MDA-MB-231 is an estrogen-independent breast cancer cell line, several studies have reported effects of tamoxifen and other ER modulators such as raloxifene in ER-negative breast cancer cell lines via activation of several intracellular signaling pathways (protein kinase C, phospholipase D) through ER-independent mechanisms [43], [44].