The advent of trastuzumab, a humanized monoclonal antibody specifically targeting the HER2 extracellular domain, has revolutionized the natural history and management of HER2-positive breast cancers [14]; (2) triple-negative breast cancer, with no expression of ER or PR and no HER2 overexpression (amplification) has overall poorer prognosis than other subtypes and requires chemotherapy [15]; (3) HER2-negative breast cancers with ER or PR expression represent the third group, called luminal breast cancers, and are usually treated with endocrine therapy [16]. The gene discussed is ESR1; the disease is breast cancer.