Based on a cellular model of interaction between HER2-positive breast cancer cell lines and CAFs from patients of the same tumour type, we aimed to identify, using a multiomics-based analysis, those candidate cytokines, proteins and miRNAs from the CAF secretome that may contribute to the development of resistance to first-line HER2-targeted therapy (trastuzumab plus pertuzumab plus docetaxel) in the tumour cell. This evidence concerns the gene ERBB2 and breast cancer.