ESR1 and breast cancer: Breast cancer is a diverse and complex disease, broadly characterized by four molecularly distinct subtypes, including luminal A, luminal B, HER2-overexpressed and triple-negative breast cancer (TNBC).64 The luminal A subtype is characterized as ER/PR-positive and HER2-negative, expressing Bcl-2, cytokeratin 8/18 and low Ki67.65 Luminal B subtypes are more aggressive ER+ breast tumors, characterized as HER2− with high Ki67, or HER2+, PR− and ER+,66 with cyclin B1 overexpression.67 The HER2 subtype is characterized by amplification of the ERBB2/HER2 gene.68