The ability of the anti-diabetic drug metformin to suppress self-renewal and proliferation of trastuzumab-resistant CSCs [33, 110, 111] is under evaluation in the METTEN study, a phase II, randomized, open-label, multicentric trial of neo-adjuvant chemotherapy and trastuzumab with or without metformin in women diagnosed with HER2-positive primary BC [112]. This evidence concerns the gene ERBB2 and breast cancer.