Prognostic Impact and Clinical Relevance of Tumor-associated Proteases in Breast Cancer

The relative impact of prognostic factors on disease-free and overall survival reflects their respective role in tumor biology. Breast cancer can be taken as an example to demonstrate the clinical and tumor-biological relevance of tumor-associated proteases. Receptor-bound urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 seem to play a major role in the dissolution and formation of tumor stroma. These processes are prerequisites for invasion and metastasis. The evaluation of 'classical' and new prognostic factors shows that the uPA and PAI-1 content of breast cancer tissue are strong and independent prognostic factors. High-risk patients can even be identified within the classical risk groups defined by lymph node or hormone receptor status, thus allowing a more individualized delineation of those patients at low or high risk for relapse and death, irrespective of established risk factors. Moreover it may well be possible to affect tumor invasion and metastasis by inhibiting protease action of solid tumors, which could be accomplished by disturbing the binding of proteases to tumor cell surface receptors. Since normal physiology differs from tumor cell pathophysiology only quantitatively, experimental evidence suggests that less drastic forms of therapy might be feasible.