Amplification of the human epidermal growth factor receptor-2 (HER2) gene and overexpression of the encoded protein are seen in 20-30% of breast cancers, and are associated with aggressive disease and relatively poor prognosis. Thus, HER2 represents an appropriate target for anticancer treatment and the humanized anti-HER2 monoclonal antibody Herceptin has been developed for this purpose. The efficacy of Herceptin has been confirmed in two pivotal trials-a monotherapy study in 222 women with HER2-positive metastatic breast cancer who had already received one or two chemotherapy regimens for metastatic disease and a study comparing Herceptin plus chemotherapy with chemotherapy alone in 469 patients previously untreated for metastatic disease. Herceptin monotherapy was associated with longer median response duration and survival than previous chemotherapy. Addition of Herceptin to chemotherapy increased response rates, time to disease progression and survival duration. Benefit was greatest in patients with high-level HER2 overexpression. Herceptin was well tolerated, with mild to moderate infusion-related reactions, usually seen with the first infusion only, being the most common event. Most patients respond to conventional supportive treatment. Cardiotoxicity, the most serious adverse event observed, occurred mainly in patients exposed to anthracyclines and was generally manageable. Thus, Herceptin represents a significant development in the management of HER2-positive breast cancer.