This AMPK-relatedmetabolic scenario is likely associated with the occurrence of autophagic, trastuzumab-refractoryCD44+CD24−/low mesenchymal immunophenotypes because treatment withmetformin, a partial inhibitor of autophagy due its limited ability to strongly reduce intracellularATP [94-96], issufficient to efficiently kill EMT-related CD44+CD24−/low cells andrestore trastuzumab efficacy in HER2 gene-amplified breast cancer cells withprimary resistance to HER1/2-targeting therapies [18, 97-101]. This evidence concerns the gene EGFR and breast cancer.