HER-2-positive metastatic breast cancer: trastuzumab and beyond

Background: The recognition achieved in the late 1980s of human epidermal growth factor receptor 2 as an appealing therapeutic target for breast cancer has led to the development of targeted therapies for patients with human epidermal growth factor receptor 2-overexpressing breast tumors. Objectives: The aim of the present review is to address the standard treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer patients, which is currently based on the humanized monoclonal antibody trastuzumab and to describe the new treatment options available for patients progressing on trastuzumab-based therapies. Methods: A broad literature research was performed in order to review treatments, starting from the developmental phase of trastuzumab to the most recent biologic agents being tested in human epidermal growth factor receptor 2-positive disease. Results: Trastuzumab combined with a taxane represents the first therapeutic option for human epidermal growth factor receptor 2-positive metastatic breast cancer. However, novel combinations of trastuzumab and chemotherapy still hold great interest for their remarkable activity and good tolerability. On the other hand, the dual epidermal growth factor receptor/human epidermal growth factor receptor 2 inhibitor lapatinib has been the first drug to be approved in combination with capecitabine for the treatment of patients who progress on trastuzumab-based therapies. Moreover, in the near future, trastuzumab plus another biologic agent targeting human epidermal growth factor receptor 2, either directly or indirectly, may represent an effective 'chemotherapy-free' combination for trastuzumab-refractory patients.