Herceptin: implications for breast cancer management

It appears that no further significant improvements in the survival of women with metastatic breast cancer are likely to result from the use of traditional chemotherapeutic agents. Research attempting to identify novel agents has focused on biological therapies, which can be used to target specific abnormalities in cancer cells. Human epidermal growth factor receptor-2 (HER2) is a cell membrane receptor with growth-regulating activity. Studies indicate that the 25-30% of women with breast cancer who overexpress HER2 have aggressive disease and a worse prognosis than those who do not overexpress HER2. Herceptin targets HER2 and is the first humanized monoclonal antibody approved for therapeutic use. Clinical trials have demonstrated that Herceptin is well tolerated, produces durable objective responses and improves survival in women with metastatic breast cancer. Its side-effects are generally mild to moderate and differ from those of traditional cytotoxic agents. Cardiotoxicity, the most significant adverse effect of Herceptin, is manageable in most patients using standard therapy. The likely positioning of Herceptin in the treatment of HER2-overexpressing metastatic breast cancer is in combination with paclitaxel as first-line therapy and as second- or third-line therapy when administered alone. It is likely that the exploitation of HER2 as a target for therapy and the development of Herceptin will serve as a model for the development of future biological therapies.