ESR1 and breast carcinoma: The main mechanisms that have been discovered are: activating mutations of the ESR1 gene encoding the ER protein (21); changes in the signaling pathways making breast cancer cell growth dependent on antiestrogenic ER ligand (tamoxifen) (22); the permanent loss of the ER (23); changes in signaling pathways enabling antihormone-resistant breast cancer cells to survive without estrogens or antiestrogens (24, 25).