Current and future anti-HER2 therapy in breast cancer

The therapeutic strategy for breast cancer with the use of targeted drugs is, at present, mainly focused on coping with HER2. Currently, lapatinib and trastuzumab are in widespread use. Virtually all completed and in progress clinical trials have demonstrated a significant enhancement in the rate of pathologic complete response (pCR), the primary endpoint in these studies, in cases of patients with HER2-positive breast cancer that received trastuzumab in the neoadjuvant setting. Use of lapatinib in the neoadjuvant setting should be considered experimental. When a 12-month course of trastuzumab was added to adjuvant chemotherapy, the disease-free survival (DFS) was greater and the overall survival (OS) was also greater. Although trastuzumab is approved as single-agent therapy, most patients are treated with trastuzumab plus cytotoxic agents. Trastuzumab, administered as single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Dual targeting approach with a combination of trastuzumab and lapatinib improved progression-free survival (PFS) as compared with lapatinib alone in patients with metastatic breast cancer who have not had a response to trastuzumab. The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged PFS. Novel anti-HER2 targeted therapies are needed to utilise novel approaches to combat trastuzumab resistance.