Although approximately 70% of breast cancers are ERα positive, and endocrine therapy with agents such as tamoxifen, a selective estrogen receptor modulator [45], and aromatase inhibitors [46], which ablate peripheral estrogen synthesis, can substantially improve disease-free survival, most ERα-positive tumors that initially respond to anti-estrogenic reagents treatment develop resistance to these treatments without any alteration in the ER expression profile [47]. This evidence concerns the gene ESR1 and breast cancer.