Invasion factors
urokinase-type plasminogen activator (uPA) and its
plasminogen activator inhibitor (PAI-1) are the only novel
tumor biological prognostic factors validated at the highest level of evidence with regard to their clinical utility in
breast cancer.
Antigen levels of both factors present in extracts of primary
tumor tissue are determined by standardized, quality-assured
enzyme-linked
immunosorbent assays. Numerous studies showed that patients with low levels of uPA and
PAI-1 have a significantly better survival than patients with high levels of either factor. Recently, these data have been validated by a European Organization for Research and Treatment of
Cancer pooled analysis comprising more than 8000
breast cancer patients. The particular combination of both factors, uPA/PAI-1 (both low vs. either or both factors high), outperforms the single factors as well as other traditional prognostic factors with regard to risk group assessment, particularly in node-negative
breast cancer. Node-negative
breast cancer patients with low levels of uPA and
PAI-1 have a very good prognosis and, as such, may be candidates for being spared the burden of
adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at a substantially increased risk of relapse, comparable to that of patients with > or = 3 involved axillary lymph nodes. First results from a multicenter prospective randomized
therapy trial in node-negative
breast cancer (Chemo N(0)) as well as recent retrospective analyses indicate that these high-risk patients benefit from
adjuvant chemotherapy. Thus, combined determination of the invasion factors uPA and
PAI-1 supports risk-adapted individualized therapeutic strategies in patients with primary
breast cancer, particularly in those with node-negative
breast cancer.