The frequency of ER expression in these HER2 heterogeneous cases was significantly higher than that found in the HER2-positive breast cancers included in The Cancer Genome Atlas (TCGA; 56/79, 71%) dataset [10], the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) discovery (40/72, 56%) and validation (24/61, 39%) datasets [26], and the 1 year adjuvant trastuzumab versus observation for HER2-positive breast cancer (HERA) trial [27] cohort (1,536/3,383, 45%) (Fisher’s exact test, two-tailed, P = 0.0326, P = 0.0026, P < 0.0001, P < 0.0001, respectively). This evidence concerns the gene ESR1 and breast carcinoma.