The Phase II neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer (METTEN) study studied neoadjuvant metformin, in combination with trastuzumab and paclitaxel, in early stage, HER2+ breast cancer and showed the combination was safe, with no significant toxicities attributable to metformin, and that metformin provided additional treatment benefit[126]. Here, ERBB2 is linked to breast cancer.