The mechanisms underlying endocrine resistance are highly complicated, involving mutations affecting various genes (such as ER, aromatase, and tyrosine kinase receptor) and signaling pathways (such as phosphatidylinositol 3-kinase and mitogen-activated protein kinase), variations in transcription factors (such as MYC, FOXA1, CTCF, or TBX3), epigenetic changes, metabolic reprogramming of tumor cells, or tumor microenvironment changes10. This evidence concerns the gene ESR1 and neoplasm.