Based on molecular profiling and the presence of estrogen (ER), progesterone (PR), and HER2 receptors, as well as the intensity of Ki-67 protein expression, breast cancers are categorized into five principal molecular subtypes: Luminal A ([ER+/PR+] HER2-Ki67−), luminal B ([ER+/PR+] HER2-KI67+) or ([ER+/PR+] HER2+KI67+), HER2 over-expression ([ER−/PR−] HER2+), basal ([ER−/PR−] HER2−, basal marker+), and normal-like ([ER+|PR+] HER2-KI67−), which shares a similar immunohistochemical (IHC) status with the luminal A subtype, but is characterized by normal breast tissue profiling [3]. This evidence concerns the gene ESR1 and breast cancer.