In this view, just as HR + /HER2- BC is endocrine therapy sensitive and most-often in a Luminal A/B transcriptional state and HR-/HER2 + BC is endocrine therapy insensitive and most-often in a HER2-E transcriptional state, certain RTK/MAPK oncogenic drivers might be able push HR + /HER2- MBC tumors to a HER2-E transcriptional state that is endocrine therapy insensitive. This evidence concerns the gene HR and breast cancer.