ESR1 and breast cancer: In clinical practice, immunohistochemical quantification of Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) is the gold standard to classify breast cancer into hormone receptor positive (HR+), HER2 positive (HER2+) and triple negative breast cancer (TNBC), whereas transcriptional profiling stratifies breast cancer into five major subtypes, i.e. luminal A, luminal B, HER2 over-expression, basal, and normal-like tumors primarily overlapping clinical subtypes (4).