However, it is known that over time, breast cancer often develops resistance to drug therapy, that can be traced to several mechanisms, such as mutations in the estrogen receptor, altered expression of the same receptor (epigenetic modifications), changes in the levels of metabolic enzymes involved in hormone synthesis and aberrant activation of signal transduction pathways (up- regulation of PI3K, MAPK, CDKs) [25, 26]. This evidence concerns the gene ESR1 and breast carcinoma.