ESR1 and breast cancer: However, as indicated earlier, due to lack of ER-α or functionalinactivation of ER-α via complex epigenetic paradox45, 56, 57, 58, 60, 63, 64 or other mechanisms, some BC cells becomeTam-resistant,13, 48, 51, 52, 64 resulting in an enormoustherapeutic burden.