According to established clinicopathological factors, approximately 70% of breast cancer patients without axillary node involvement belong to the group of patients with an intermediate risk of recurrence. In such patients with endocrine responsive disease, the current guidelines suggest either adjuvant chemo-endocrine therapy or endocrine therapy alone. The challenge is therefore to identify those patients who will not need adjuvant chemotherapy due to their very low risk of recurrence. The plasminogen activator system is a complex system with multiple functions, e.g. cell invasion, angiogenesis and senescence, in a variety of solid tumors. Increased levels of the invasion factors uPA (urokinase-type plasminogen activator) and/or its inhibitor PAI-1 in primary breast cancer tissue have been correlated with a poor outcome. The clinical utility of uPA/PAI-1 has been proven at the highest level of evidence (LoE-1). In the evidence-based, annually updated AGO guidelines on breast cancer management, the German Working Group for Gynecological Oncology (AGO) recommended a combination of both biomarkers as risk-group-classification markers for routine clinical decisions. In addition to being clinically useful for prognostic assessment, the biomarkers may also serve as predictive factors predicting the response to adjuvant chemotherapy. Moreover, specific compounds that interact with the uPA/PAI-1 system are currently in phase II/III development for the treatment of several cancer entities. The ongoing NNBC 3-Europe trial is aimed at validating uPA/PAI-1 for clinical routine risk assessment and optimizing adjuvant chemotherapy in node-negative high-risk patients. The development and transfer of basic research data for uPA/PAI-1 into clinical practice in two evidence-based clinical trials represents an excellent example of successful translational research.
«According to established clinicopathological factors, approximately 70% of breast cancer patients without axillary node involvement belong to the group of patients with an intermediate risk of recurrence. In such patients with endocrine responsive disease, the current guidelines suggest either adjuvant chemo-endocrine therapy or endocrine therapy alone. The challenge is therefore to identify those patients who will not need adjuvant chemotherapy due to their very low risk of recurrence. The plas...
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