Plasminogen Activator Inhibitor Type 1 is the Most Significant of the Usual Tissue Prognostic Factors in Node-Negative Breast Ductal Adenocarcinoma Independent of Urokinase-Type Plasminogen Activator

2008 ◽  
Vol 8 (2) ◽  
pp. 168-177 ◽  
Author(s):  
Françoise Descotes ◽  
Benjamin Riche ◽  
Simone Saez ◽  
Guy De Laroche ◽  
Jean Datchary ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Ductal Adenocarcinoma ◽  
Node Negative ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Clinical Relevance of Invasion Factors Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 for Individualized Therapy Decisions in Primary Breast Cancer Is Greatest When Used in Combination

2002 ◽  
Vol 20 (4) ◽  
pp. 1000-1007 ◽  
Author(s):  
Nadia Harbeck ◽  
Ronald E. Kates ◽  
Manfred Schmitt
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

PURPOSE: A strong prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor and plasminogen activator inhibitor type 1 (PAI-1) as individual factors is well established in breast cancer. The improvement in clinical risk assessment gained by combining these factors is evaluated here. PATIENTS AND METHODS: uPA and PAI-1 levels were prospectively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer. RESULTS: In the clinically important subgroup of node-negative patients without adjuvant systemic therapy (n = 269; median follow-up, 60 months), the clinical value of testing both uPA and PAI-1 is demonstrated. The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group. uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival; patients with high uPA/PAI-1 have an increased relapse risk (P < .001; relative risk, 4.8; 95% confidence interval [CI], 2.5 to 9.1), in particular for early relapse. Even within risk groups stratified by established criteria (nodal or menopausal status, tumor size, grade, or steroid hormone receptors), uPA/PAI-1 provides significant risk group discrimination. In the whole collective, the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1. CONCLUSION: The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination. The particular combination of uPA and PAI-1 (both low v either or both high) is superior to either factor alone and supports risk-adapted individualized therapy decisions.

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