Abstract: Human epidermal growth factor receptor 2 （HER2） is a transmembrane tyrosine kinase receptor which can activate the downstream signaling pathways， leading to proliferation and survival of cancer cells. HER2 positive breast cancer is a special subtype of breast cancer with high malignancy and poor prognosis. Trastuzumab， an antiHER2 monoclonal antibody， is able to improve the treatment efficacy of this kind of cancer， but could not escape the ending of resistance ultimately. In recent years， researches on mechanism of trastuzumab resistance， development of novel targeted drugs and exploration of the treatment strategies have made significant progress in overcoming the resistance of trastuzumab. This article is going to introduce strategies of targeted therapy and also the data of clinical trials focusing on the treatment against trastuzumab resistance.

Key words: Metastatic breast cancer, Human epidermal growth factor receptor 2（HER2）, Drug resistance, Targeted therapy