Mechanistically, although the multifaceted mechanisms have been proposed as driving BC growth and progression, the involvement of functionally active classical ER-α is debatable because classical ER-α expression in BC is an indicator of a good prognosis with less aggressive behaviors [82–84], where ER-α is dysfunctional in a metastatic micro-environment and is hormone resistant [85]. The gene discussed is ESR1; the disease is breast cancer.