In the following sections of the article, we briefly discuss the cellular, pre-clinical, and clinical studies that are currently testing metformin as a monotherapy or in combination with other chemotherapeutic drugs or phytochemicals/natural compounds for its efficacy as an anti-cancer/anti-tumor agent in the treatment of estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive types of breast cancers, and triple negative breast cancers (TNBCs) [135]. The gene discussed is ESR1; the disease is cancer.