ERBB2 and breast cancer: In our current CSC-based framework of primary resistance to trastuzumab in cHER2+ BC, genetic (i.e., mutational landscape) and non-genetic (i.e., epigenetic and microenvironmental) mechanisms collectively but differentially contribute to tumor heterogeneity of cHER2+ tumors belonging to each molecular subtype of cHER2+ BC (i.e., luminal A/cHER2+, luminal B/cHER2+, HER2-enriched/cHER2+, basal/cHER2+, and claudin-low/cHER2+; Figure B1-1).