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Breast carcinoma is moderately sensitive to multiple antitumor agents and combinations of medicines produce higher response rates and longer durations of response and survival than single-agent therapy. Within the past decade a number of new agents have been developed and proved effective in the treatment of breast cancer. The most prominent are the taxanes, including paclitaxel and docetaxel. These taxanes are currently being used in combination with other active medicines including the anthracyclines, cisplatin and its analogs, alkylating agents, antimetabolites, Vinca alkaloids, and anti-estrogens. Recent advances in our understanding of the basic biology of breast carcinoma, including the internal and external stimuli that result in malignant transformation, progression, transformation, and metastasis, have provided additional potential targets for therapeutic intervention.

More specifically, growth factor receptors, including the EGF receptor, have been targeted with a variety of treatment strategies. Monoclonal antibodies specific for each of these receptors have been developed and the first to undergo complete preclinical and clinical evaluation was the anti-HER- 2 monoclonal antibody, trasluzumab (Herceptin). This antibody binds with high affinity to the extracellular domain of HER-2 and inhibits transmission of the growth- stimulatory signal. Other approaches to target HER-2 have included the development of tyrosine kinase inhibitors as well as other signal transduction inhibitors (vaccines, gene therapy, and antisense therapy). The tyrosine kinase inhibitor emodin has been shown to suppress growth of HER-2/neu- overexpressing breast cancer cells in athymic mice and to actually sensitize these cells to paclitaxel. Another class of compounds, the 4-anilinoquinazolines, has been shown to selectively target and irreversibly inactivate the EGF receptor tyrosine kinase through specific covalent modification of a cysteine residue present in the ATP –binding pocket of this enzyme. These new cytotoxic agents and antitumor strategies thus offer promising treatment options for patients with metastatic breast carcinoma.