The next generation of biologic agents: therapeutic role in relation to existing therapies in metastatic breast cancer.

The use of more active cytotoxic agents (eg, anthracyclines and taxanes) in the adjuvant setting has impacted treatment options in metastatic breast cancer (MBC). Various new approaches to combination therapy are being investigated, including classic and novel cytotoxic agents and targeted therapies. The heterogeneous molecular pathways involved in the development of breast cancer provide numerous potential targets for therapeutic intervention. Molecular technologies have facilitated the development of various new therapies targeted at disrupting processes as diverse as angiogenesis and DNA repair. Targeted therapies have the potential to improve outcomes in MBC, and their use has increased dramatically over recent years after the introduction of human epidermal growth factor receptor 2 (EGFR2)-targeted therapy with trastuzumab. Lapatinib and bevacizumab have recently been approved for patients with MBC. Numerous other targeted agents are undergoing preclinical investigation or are being evaluated in clinical trials. The maximum benefit of targeted therapies has been realized by their combined use with cytotoxic agents. Overall, single-agent use of targeted therapies has failed to produce dramatic benefit in patients with advanced breast cancer. This article reviews the data from studies of established and emerging targeted therapies in the treatment of MBC and describes how best to incorporate these agents into current treatment paradigms.