Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer.

Abstract

Combined determination of urokinase-type plasminogen activator (uPA) and its inhibitor, activator inhibitor type 1 (PAI-1), supports risk-adapted individualized therapy concepts, particularly in node-negative breast cancer. The prognostic impact of both factors in primary breast cancer was substantiated by a pooled analysis of > 8000 patients with breast cancer and a multicenter prospective randomized therapy trial in node-negative breast cancer; findings achieved the highest level of evidence for tumor biomarkers. Patients with node-negative breast cancer with low antigen levels of uPA and PAI-1 in their primary tumor tissue have a very good prognosis and therefore may be spared the burden of adjuvant chemotherapy, whereas those with elevated uPA/PAI-1 antigen levels carry an increased risk of disease recurrence. Recent retrospective analysis of > 3000 patients indicated that patients with breast cancer with high uPA/PAI-1 values derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1 levels. Similarly, in the multicenter prospective Chemo N0 trial, administration of cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy led to a substantial reduction in risk of disease recurrence in patients with high uPA/PAI-1. However, benefit from adjuvant endocrine therapy appears to be independent of a patient's uPA/PAI-1 status. In metastatic breast cancer, retrospective studies showed that elevated uPA or PAI-1 present in the primary tumor tissue are associated with a poor response to later palliative endocrine therapy. These findings suggest that high levels of uPA and/or PAI-1 do reflect an aggressive phenotype that may be overcome or suppressed by early systemic therapy in the adjuvant setting but may be too advanced for response to palliative therapy at a later stage.

• Authors: Nadia Harbeck, Roanld E Kates, Manfred Schmitt, Katja Gauger, Marion Kiechle, Fritz Janicke, Christoph Thomassen, Maxime P Look, John A Foekens
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 5 Issue 5 Pg. 348-52 (Dec 2004) ISSN: 1526-8209 [Print] United States
• PMID: 15585071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Plasminogen Activator Inhibitor 1
• Urokinase-Type Plasminogen Activator

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (diagnosis, drug therapy, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Neoadjuvant Therapy
• Plasminogen Activator Inhibitor 1 (analysis)
• Prognosis
• Randomized Controlled Trials as Topic
• Treatment Outcome
• Urokinase-Type Plasminogen Activator (analysis)