With overexpression of HER2 receptors driving proliferation, survival, and invasion of breast tumors, HER2-positive breast cancers (HER2 +/ER + or PR + or PR + or ER +/PR +; HER2 +/ER-/PR-) account for 15–20% of all cases (40, 41). The gene discussed is ESR1; the disease is breast cancer.