ESR1 and neoplasm: While HER2 testing by immunohistochemistry and fluorescence in situ hybridization (FISH) and hormone receptor (HR) status are still the gold standard for treatment recommendation, tumor intrinsic features, mainly HER2-addiction [i.e., PAM50, TRAR, estrogen receptor (ER)] and tumor microenvironment features (i.e., tumor infiltrating lymphocytes and immune signatures), have been defined as predictive and/or prognostic biomarkers across multiple clinical trials of anti-HER2 therapies (reviewed in [2,3,4,5]) in accordance with the mechanisms of action of trastuzumab [6].