This is underscored by the findings of the 2020 update guideline from the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) that acknowledged that limited data have shown the benefit of endocrine therapy for tumors with ER 1–10% expression, which were termed “ER-low positive breast cancer” [165,166]. The gene discussed is ESR1; the disease is breast cancer.