Recent developments in breast cancer therapy.

Over the past three decades conceptual approaches to breast cancer have led to improvements in locoregional therapy and early diagnosis. Systematic screening programs with mammography reduce disease-specific mortality by 25% to 30%, while many patients with early breast cancer receive optimal breast-conserving treatments. Our increased understanding of the biology of breast cancer helped develop successful adjuvant systemic therapies (cytotoxic and hormonal) that, in turn, reduce mortality by 15% to 25%. Newer therapeutic interventions are under intensive investigation. While continued progress in cytotoxic therapy is evident (taxanes, vinorelbine, gemcitabine, new antifolates, liposomal anthracyclines, etc), there is increasing interest in targeting growth factors and their receptors. Thus, a monoclonal antibody directed to the extracellular domain of the HER-2/neu oncoprotein was recently approved by the Food Drug Administration based on evidence of antitumor activity as a single agent and in combination with cytotoxic therapy. A similar approach against the epidermal growth factor receptor is under evaluation in clinical trials. Various methods of inhibiting intracellular signal transduction also are in clinical development. These include tyrosine kinase inhibition, dominant negative mutant inhibitors of GRB-2, farnesyl transferase inhibition and vaccines directed against various epitopes expressed by mammary cancer cells. Angiogenesis and the enzyme telomerase are other targets under intense scrutiny since they are integrally involved with metastases and cellular immortality, both common characteristics of the malignant cell. These lines of investigation are likely to provide innovative therapeutic interventions, which may improve the specificity and therapeutic index of anticancer treatments.