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Human epidermal growth factor receptor 2 (Her2/neu) have been found in approximately 25-30% breast tumors and its overexpression is associated with a high risk of relapse, unfavourable prognosis and short survival.Trastuzumab has shown good clinical response in breast tumors overexpressing Her2/neu.However, only a fraction of Her2 overexpressing breast tumors respond to trastuzumab and after the initial response the resistance to trastuzumab is likely to be developed within one year.Platelet-derived growth factor receptors (PDGFR) α and β are linked with advanced human breast cancers and PDGFRs produced in carcinomas are generally thought to act on the nonepithelial tumor stroma by promoting angiogenesis.Still it is unclear how expression of PDGFRs contributes to the resistance to trastuzumab.We therefore have assessed interactions between epithelial breast cancer cells and human fibroblasts upon trastuzumab treatment in a co-culture model.We have examined sensitivity of trastuzumab on Her2-positive breast carcinoma SKRB3 cells and SKRB3 cells co-cultured with fibroblasts.We have also assessed effects of PDGFRs on trastuzumab treated SKRB3 co-cultured with fibroblasts.We found that Her2 overexpessing SKRB3 cells but not BJH-Tert cells derived from human fibroblasts respond to trastuzumab.This indicating that effect of trastuzumab on these cells is Her2-dependent and this is in agreement with previously published data.Major finding of present study is that presence of PDGFRs can minimise efficacy of trastuzumab in SKRB3 co-cultured with BJH-Tert cells.