Invasion Factors uPA/PAI-1 and HER2 Status Provide Independent and Complementary Information on Patient Outcome in Node-Negative Breast Cancer

2003 ◽  
Vol 21 (6) ◽  
pp. 1022-1028 ◽  
Author(s):  
Iris Zemzoum ◽  
Ronald E. Kates ◽  
Jeffrey S. Ross ◽  
Peer Dettmar ◽  
Moshumi Dutta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Tumor Tissue ◽  
Her2 Status ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Long Term Follow Up ◽  
Pai 1

Purpose: The independent clinical relevance of invasion factors urokinase-type plasminogen activator (uPA)/PAI-1 and HER2 status was evaluated in lymph node-negative breast cancer patients (N = 118) without adjuvant systemic therapy after long-term follow-up of more than 10 years (median, 126 months). Patients and Methods: Levels of uPA and its inhibitor PAI-1 were prospectively measured by enzyme-linked immunosorbent assay in primary tumor tissue extracts. HER2 gene amplification (HER2_AMP) was evaluated by fluorescence in situ hybridization (FISH; Ventana Medical Systems HER-2/neu probe; Tucson, AZ), and HER2 protein overexpression (HER2_EXP) was evaluated by immunohistochemistry (IHC; Oncogene Science antibody Ab-3; Cambridge, MA) on parallel-cut formalin-fixed paraffin-embedded tissue sections. Results: uPA/PAI-1 was high (either one or both factors were high) in 44% of the tumors. HER2_AMP was detected by FISH in 33% of the patients, and HER2_EXP was found by IHC in 44% of the patients. In a multivariate analysis of established and tumor-biologic prognostic factors, uPA/PAI-1 was the only independent prognostic factor for disease-free survival ([DFS]; P < .001; relative risk [RR], 8.3; 95% confidence interval [CI], 3.4 to 20.4). Although HER2_AMP and HER2_EXP did not reach significance for DFS, they were significant for overall survival (OS), even in multivariate analysis (HER2_AMP: P = .004; RR, 3.7; 95% CI, 1.5 to 9.2; HER2_EXP: P = .009; RR, 3.4; 95% CI, 1.4 to 8.7). Conclusion: After long-term follow-up, uPA/PAI-1 levels in primary tumor tissue reliably and strongly indicate an aggressive course of disease in lymph node-negative breast cancer independent of HER2 status. The particular prognostic effect of HER2 status on OS may reflect its ability to predict resistance to systemic therapy.

Omitting axillary lymph node dissection in sentinel node negative breast cancer patients is safe: A long term follow-up analysis

2004 ◽  
Vol 88 (1) ◽  
pp. 4-7 ◽  
Author(s):  
Hans Torrenga ◽  
Hans Fabry ◽  
Joost R.M. van der Sijp ◽  
Paul J. van Diest ◽  
Rik Pijpers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Node Dissection ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Long Term Follow Up

Disease-free interval and estrogen receptor activity in tumor tissue of patients with primary breast cancer: analysis after long-term follow-up

1985 ◽  
Vol 6 (2) ◽  
pp. 123-130 ◽  
Author(s):  
J. M. M. Raemaekers ◽  
L. V. A. M. Beex ◽  
A. J. M. Koenders ◽  
G. F. F. M. Pieters ◽  
A. G. H. Smals ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Tissue ◽  
Disease Free Interval ◽  
Free Interval ◽  
Estrogen Receptor Activity ◽  
Long Term Follow Up ◽  
Disease Free

scholarly journals Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

2016 ◽  
Vol 51 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Nina Fokter Dovnik ◽  
Iztok Takac
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Multivariate Model ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Size Grade ◽  
Pai 1

Abstract Background The association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients. Patients and methods A retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000–2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model. Results In univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83–4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low. Conclusions uPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.

Long-Term Follow-Up Confirms Prognostic Impact of Pai-1 and Cathepsin D and L in Primary Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 79-83 ◽  
Author(s):  
N. Harbeck ◽  
U. Alt ◽  
U. Berger ◽  
R. Kates ◽  
A. Krüger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Cathepsin D ◽  
Cathepsin L ◽  
Lymph Node Status ◽  
Prognostic Impact ◽  
Long Term Follow Up ◽  
Pai 1

After long-term follow-up, the prognostic impact of the following proteolytic factors associated with tumor invasion and metastasis was evaluated in 276 primary breast cancer patients: uPA (urokinase-type plasminogen activator), PAI-1 (uPA inhibitor type 1), and cathepsins B, D and L. The median follow-up of patients still alive at the time of analysis was 109 months. To date 119 patients (43%) have relapsed and 117 (42%) have died. Antigen levels of uPA and PAI-1 were determined by ELISA in detergent extracts; cathepsin B, D, and L content was determined in cytosol fractions of the primary tumor: cathepsin D by ELSA and cathepsin B and L by ELISA. In multivariate analysis (Cox model) for disease-free survival (DFS), lymph node status (p<0.001; RR=3.8), cathepsin L (p<0.001; RR=2.6) and PAI-1 (p=0.027; RR=1.7) were significant factors in all patients. In addition to these factors, grading was significant for overall survival (OS). In another multivariate approach, CART (Classification And Regression Trees) analysis, lymph node status (p<0.001) turned out to be the strongest discriminator for patients at high risk of relapse. In the node-negative patient subset, PAI-1 was the strongest risk group discriminator (p<0.001): in this subset, patients with low levels of both PAI-1 and cathepsin D had a very low relapse rate of only 3.2% compared to 39% in the remaining node-negative patients. In node-positive patients cathepsin L gave the best risk group assessment (p=0.001). In conclusion, tumor-associated PAI-1 and cathepsins D and L provide significant, statistically independent prognostic information for DFS and OS in primary breast cancer, even after a median follow-up period of almost 10 years.

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.

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