The future applications of DNA and RNA technology to prognosis and predicition in breast cancer

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Adjuvant systemic therapy has been shown to reduce relapses and prolong survival in treated women with operable breast cancer. This is true for all subpopulations (i.e., node-positive and node-negative disease, premenopausal and post-menopausal ages). The overall effect of the adjuvant systemic therapies is modest (i.e., a relative reduction in risk of mortality of 20-25%; a relative reductive in the risk of relapse of 3@40%]. Adjuvant endocrine therapies include tamoxifen and, ovarian ablation. Adjuvant chemotherapy regimens mainly include CMF or anthracycline-containing combinations. The use of the two modalities (endocrine and cytotoxic therapies) together has proven to be more beneficial than each modality alone, but optimal combinations are still under investigation. Adjuvant systemic therapy is typically administered after surgery, tailored according to prognostic features obtained by histopathological examinations. Preoperative systemic therapy has been successfully used in patients with locally advanced disease. Experimental models have provided the basis for primary systemic therapy in operable breast cancer, but only a few clinical investigations have been properly conducted in this setting. The largest clinical trial of preoperative versus postoperative systemic treatment is the NSABP Trial B-18 with more than 1700 patients, the results of which are not yet available. It is clear that preoperative chemotherapy provides a larger proportion of patients with the opporumity to have breast conservation. It remains uncertain whether all patients will benefit from primary systemic therapy in terms of disease freedom and overall survival. Future investigations should provide information on: l Biological (and endocrine) events which influence responsiveness to each of the treatment modalities. l Features which predict usefulness of preoperative systemic therapy. l Definition of pre- and post-surgical adjuvant treatment strategies. l Novel and more efficacious cytotoxic combinations for both pre- and post-surgical adjuvant treatments.