Clinical data extracted from drug trials have shown that metformin does show synergistic apoptotic effects when used with chemotherapeutic agents in BC.50,107 Furthermore, when metformin is used as a single-agent, it may trigger cell cycle arrest in both oestrogen receptor positive (ER+) and ER-negative (ER–) BCs cells.108,109 Metformin also elicits toxic effects on cancer stem cells, but not on normal stem cells. This evidence concerns the gene ESR1 and breast cancer.