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Standards and future strategies in adjuvant chemotherapy treatments

Breast cancer is an increasing global public health burden with more than 1 million new cases anticipated worldwide and more than 200,000 new cases anticipated in the United States in 2007. Screening and awareness have increased the detection of breast cancer at its early stages where it is most curable, but many such patients have microscopic metastatic disease even when diagnosed. The outcome for such patients can only be improved through the effective control of this undetected systemic disease, thus motivating adjuvant therapy. For patients with sufficient risk, based historically on nodal status, tumor size, specific histology, and hormone receptor status, chemotherapy can be the only option or a component of regimens including hormonal agents and anti-HER2 drugs. Genetic profiling is a recent addition to our risk stratification methods and can allow for more precise selection of chemotherapy. Historical chemotherapy regimens were largely empiric combinations of drugs with proven activity in advanced disease. More recent advances have been translational, with preclinical development of the taxanes leading to their testing in the adjuvant setting and mathematical modeling leading to improvements in the delivery of otherwise standard agents. Despite this mixture of empiricism and translational research, adjuvant chemotherapy is highly effective, particularly in selected subsets of patients, such as those with no expression of hormone receptors. Building on the demonstration of activity for the humanized monoclonal anti-HER2 antibody (trastuzumab) as adjuvant treatment, newer HER2 targeting drugs are in development and will be tested in this setting (lapatinib). For the majority of tumors lacking overexpression of HER2, planned research focuses on anti-angiogenic agents (bevacizumab). For many patients, an optimized chemotherapy plan (that is, dose-dense administration of anthracyclines and taxanes) combined with appropriate targeted agents is likely to offer even larger improvements in outcomes than those already achieved.

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Hudis, C., McArthur, H. Standards and future strategies in adjuvant chemotherapy treatments. Breast Cancer Res 9 (Suppl 1), S16 (2007).

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