scholarly journals Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients

1999 ◽  
Vol 79 (7-8) ◽  
pp. 1190-1198 ◽  
Author(s):  
J H de Witte ◽  
C G J Sweep ◽  
J G M Klijn ◽  
N Grebenschikov ◽  
H A Peters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Pai 1

Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers

2002 ◽  
Vol 30 (2) ◽  
pp. 207-210 ◽  
Author(s):  
M. J. Duffy
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Prospective Trial ◽  
Axillary Node ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Pai 1

Urokinase-type plasminogen activator (uPA) is a serine protease that is causally involved in cancer progression, especially invasion and metastasis. Multiple studies have shown that breast cancer patients whose primary cancer contains high levels of uPA have a significantly worse outcome than patients with low levels. As a prognostic marker for breast cancer the information supplied by uPA is both independent of traditionally used factors and significant in the important subgroup of axillary-node patients. Paradoxically, high levels of plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of uPA, also predict for aggressive disease. Recently, the prognostic impact of both uPA and PAI-1 in axillary node-negative breast cancer was confirmed using two different Level 1 Evidence studies, i.e. in both a randomized prospective trial and a pooled analysis. Therefore, uPA and PAI-1 appear to have fulfilled all the criteria for the routine assessment of prognosis in newly diagnosed breast cancer patients

Urokinase-type plasminogen activator in plasma from breast cancer patients

1988 ◽  
Vol 24 (9) ◽  
pp. 1553
Author(s):  
F. Bach ◽  
J. Grøndahl-Hansen ◽  
N. Agerlin ◽  
P. Munkholm-Larsen ◽  
L.S. Nielsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Breast Cancer Patients ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer

2004 ◽  
Vol 91 (03) ◽  
pp. 450-456 ◽  
Author(s):  
Ronald Kates ◽  
Katja Gauger ◽  
Amina Willems ◽  
Marion Kiechle ◽  
Viktor Magdolen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Tissue ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Low Levels ◽  
Pai 1

SummaryUrokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, play a key role in tumor invasion and metastasis. They were the first novel tumor biological factors to be validated at the highest level of evidence (LOE I) regarding their clinical utility in breast cancer. Their antigen levels are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA and PAI-1 in their primary tumor tissue have a significantly better survival than patients with high levels of either factor. These prognostic data have recently been validated by an EORTC (European Organization for Research and Treatment of Cancer) pooled analysis comprising more than 8,000 breast cancer patients. In addition, results from a multicenter prospective randomized therapy trial in node-negative breast cancer (“Chemo N0”) showed that node-negative breast cancer patients with low levels of uPA and PAI-1 in their primary tumor have a very good prognosis, and may thus be candidates for being spared the burden of adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at substantially increased risk of disease recurrence, comparable to that of patients with three or more tumor cell positive axillary lymph nodes. The “Chemo N0” trial as well as retrospective data also indicate that these high-risk patients benefit from adjuvant chemotherapy. In conclusion, over a period of about 15 years sufficient evidence has been put forward to demonstrate that determination of uPA and PAI-1 in primary breast cancer patients supports risk-adapted individualized therapy decisions, particularily in patients with node-negative disease.

scholarly journals Tumor-Biological Factors Upa and PAI-1 as Stratification Criteria of a Multicenter Adjuvant Chemotherapy Trial in Node-Negative Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 73-78 ◽  
Author(s):  
A. Prechtl ◽  
N. Harbeck ◽  
C. Thomssen ◽  
C. Meisner ◽  
M. Braun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Plasminogen Activator ◽  
Systemic Therapy ◽  
Axillary Node ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Pai 1

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

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