In endocrine therapy, a widely used treatment for hormone receptor-positive (HR+) breast cancer [50], several mechanisms of resistance have been identified, including loss of estrogen receptor α (ERα) expression, mutations and post-translational modifications of ERα, deregulation of ERα co-activators, and mutations in cancer-associated pathways, such as the cell cycle, tyrosine kinase signaling, and apoptosis [51]. The gene discussed is ESR1; the disease is cancer.