Targeted Therapy for Breast Cancer: A Focus on HER2/neu and Antiangiogenic Therapy

Breast cancer is the most common female cancer in the USA and is the main cause of death in women aged 45–55 years. Despite advances in both diagnosis and treatment, an estimated 182,460 new cases (26% of all cancers) and 40,480 deaths are expected in 2008. One area of rapid evolution is the treatment of patients with HER2/neu overexpressing breast tumors, who comprise 25–30% of all breast cancers in the early stage setting. In conjunction with chemotherapy, trastuzumab has shown efficacy in both adjuvant and metastatic settings with improved response rate, time to progression, and overall survival. Lapatinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for trastuzumab-resistant disease in combination with capecitabine; multiple studies are evaluating lapatinib in combination with other chemotherapy agents as well as targeted biologic therapy. Additional anti-HER2/neu-targeted agents under study include immunotoxins, alternate antibodies, new TKIs, and new targeted therapies such as heat shock protein inhibitors. Antiangiogenic therapy is a second successful targeted biologic therapy for the treatment of breast cancer. Bevacizumab is now approved in combination with paclitaxel to treat advanced disease, and ongoing trials are investigating bevacizumab alone or in combination in both the early- and late-stage settings. Multiple other antiangiogenic agents are in clinical trials. This chapter will review current clinical data on HER2 and antiangiogenic biologic therapies in the treatment of breast cancer.