ESR1 and breast carcinoma: There are schematically three main histologic types of breast cancer (Figure 1): i) estrogen-dependent breast cancers expressing the estradiol receptor (ER) and treated with a panel of drugs that target the estradiol receptor pathway [5]; ii) breast cancers overexpressing the human epidermal growth factor receptor 2 (HER2) oncoprotein and treated with anti-HER2-based chemotherapies, the first anti-HER2 being a therapeutic monoclonal antibody, trastuzumab [6]; and iii) “triple negative” breast cancers which lack the expression of the estradiol receptor, the progesterone receptor, and HER2.