[u-Plasminogen activator (urinary plasminogen activator, urokinase) (uPA) and its PA-1 type 1 inhibitor are not only prognostically but also predictively significant and support clinical decisions on therapy in primary carcinoma of the breast].
uPA and PAI-1 are the first novel tumor biological prognostic factors in breast cancer for which the prognostic impact has been validated at the highest level of evidence and hence all evaluation criteria for transfer into clinical practice have been fullfilled. Breast cancer patients with high uPA and/or PAI-1 levels in their primary tumor tissue have a significantly lower chance for cure than patients with low levels of both uPA and PAI-1. Our research that was honored with the Schmidt-Matthiesen-Award 2002 shows for the first time that uPA and PAI-1 are not only prognostic factors but also have a predictive impact with regard to response to adjuvant chemotherapy. Patients with high uPA/PAI-1 derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1. Benefit from adjuvant endocrine therapy is independent of uPA/PAI-1 status. The resulting question about the optimal chemotherapy for patients with high uPA/PAI-1 is currently being addressed in Germany by the NNBC-3 trial in node-negative breast cancer (AGO, EORTC-RBG) as well as the ADEBAR trial in patients with 4 or more involved axillary lymph nodes. Moreover, our results suggest the use of novel therapeutic agents interfering with the uPA system together with conventional chemotherapy in patients with high uPA/PAI-1 already in early stage disease.
Harbeck
N
N
Frauenklinik der Technischen Universität München, Germany. nadia.harbeck@lrz.tum.de
Thomssen
C
C
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator