The anti-HER2 monoclonal antibody Herceptin<sup>® </sup>demonstrates significant clinical benefits in patients with HER2-positive metastatic breast cancer (MBC). However, the combination of Herceptin plus anthracyclines, although efficacious, demonstrated a higher than expected incidence of cardiotoxicity. Therefore, studies are currently investigating Herceptin in combination with alternative anthracyclines, such as epirubicin and liposomal doxorubicin. Investigators are also beginning to examine the potential of Herceptin plus hormonal therapy, a combination that will delay the need to use cytotoxic chemotherapy. Furthermore, a plethora of novel agents have been developed that target the processes of tumorigenesis, including HER1 tyrosine-kinase inhibitors, farnesyl-transferase inhibitors, and cyclooxygenase 2 (COX2) inhibitors. Preclinical data demonstrate that the combination of Herceptin with these agents can produce at least additive effects and therefore a rationale exists to investigate these regimens in the clinical setting. As a result of the targeted nature of these agents, it is anticipated that such strategies will have favorable safety profiles. It is poss
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