Clinical relevance of prognostic factors in axillary node-negative breast cancer.

In node-negative breast cancer, advices for adjuvant therapy are based on traditional factors like age, tumour size, grade of differentiation, and steroid hormone receptor status. Several new factors that may better describe tumour behaviour, like proliferation rate (determined by thymidine labelling index, S-phase fraction, mitotic index, or Ki-67), presence of disseminated tumour cells, as well as expression of invasion factors (urokinase-type plasminogen activator uPA and its inhibitor PAI-1) and of cell cycle genes (cyclin E), as well as gene expression patterns ('genomic profiling') are currently discussed as future methods of risk assessment and also as tools for prediction of response to specific therapy modalities. Recommendations for routine use should be based on criteria of evidence-based medicine and on their impact on clinical decision making. Among the aforementioned factors, only the invasion factors uPA and PAI-1 have reached the highest levels of evidence and are mature enough to be transferred into clinical routine: their prognostic impact has been shown in several retrospective and prospective studies and in a pooled analysis of almost 3,500 node-negative patients. Their clinical impact was demonstrated in a prospective therapy trial. In addition, a predictive value with regard to chemotherapy efficacy has recently been supposed. Thus, in order to correctly assess the individual risk and to design an adequate adjuvant treatment plan for node-negative breast cancer patients, we recommend to use uPA and PAI-1 as additional criteria together with grading and age.