The gatekeeper mechanism here is modulation of the histone code, obtained using the lysine-specific histone demethylase (KDM) inhibitor MC3324, recently found by our group [21] to act as an “epigenetic” selective estrogen receptor down-regulator (SERD), showing anticancer activity in both in vitro and in vivo BC models [22].Via inhibition of LSD1 and UTX, MC3324 induces an epigenetic rebalance, which in turn has a major effect on mRNA, miRNA, and proteins. This evidence concerns the gene ESR1 and breast cancer.