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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 nodenegative
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.
Key words
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Article info
Publication history
Accepted:
May 10,
2004
Received in revised form:
May 10,
2004
Received:
January 14,
2004
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
