The phase 3 adjuvant lapatinib and/or trastuzumab treatment optimization (ALTTO) randomized trial reported that, while insulin administration supported cancer progression and was associated with detrimental effects, metformin-treated HER2 positive diabetic breast cancer patients presented with improved disease-free survival and overall survival rates when compared to HER2 positive diabetic breast cancer patients not on metformin treatment [155]. Here, INS is linked to cancer.