Luo et al. revealed that, in HER2+ breast cancer cell models sensitive to trastuzumab, IGF2/IGF-1R/IRS1 oncogenic signaling is kept at bay by a negative feedback loop that involves the two IRS1-targeting miRNAs, miR-128-3p and miR-30a, and an IGF2-targeting miRNA, miR-193-5p. Here, IGF1R is linked to breast carcinoma.