In support of this, a recently conducted pre-clinical study with trastuzumab-sensitive parental breast cancer cell lines (i.e., BT474 and SKBR3) and trastuzumab-resistant breast cancer sublines (i.e., BT-474-HR20 and SKBR3-pool2) showed that metformin treatment causes significantly more inhibition of proliferation and clonogenicity in trastuzumab-resistant sublines via disruption of HER2/IGF-IR complexes (which are solely present in the resistant sublines) [116]. This evidence concerns the gene IGF1R and breast cancer.