In HER2 overexpressing (tumor-initiating breast cancer stem cell-like), SKBR3 cells with an ‘acquired resistance’ to trastuzumab and JIMT-1 cells (HER2 overexpressing cells derived from the pleural metastasis of a patient who was clinically resistant to trastuzumab ab initio) with an ‘intrinsic’ refractoriness to trastuzumab, treatment with metformin (0.05 mM, 0.1 mM, 0.5 mM, and 1 mM) inhibited the MSFE and hence reduced the number and size of mammospheres in a dose-dependent manner [113,246]. This evidence concerns the gene ERBB2 and breast cancer.