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Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients

Look, MP; van Putten, WLJ; Duffy, MJ; Harbeck, N; Christensen, IJ; Thomssen, C; Kates, R; Spyratos, F; Fernö, Mårten LU and Eppenberger-Castori, S, et al. (2002) In Journal of the National Cancer Institute 94(2). p.116-128
Abstract
Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within... (More)
Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies. (Less)
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Journal of the National Cancer Institute
volume
94
issue
2
pages
116 - 128
publisher
Oxford University Press
external identifiers
  • pmid:11792750
  • wos:000173311700012
ISSN
1460-2105
DOI
10.1093/jnci/94.2.116
language
English
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yes
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3d865be1-5a19-40bc-b816-c9d1922c96f3 (old id 345780)
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2007-11-02 09:41:50
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2016-04-16 03:27:34
@article{3d865be1-5a19-40bc-b816-c9d1922c96f3,
  abstract     = {Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P&lt;.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.},
  author       = {Look, MP and van Putten, WLJ and Duffy, MJ and Harbeck, N and Christensen, IJ and Thomssen, C and Kates, R and Spyratos, F and Fernö, Mårten and Eppenberger-Castori, S and Sweep, CGJF and Ulm, K and Peyrat, JP and Martin, PM and Magdelenat, H and Brunner, N and Duggan, C and Lisboa, BW and Bendahl, Pär-Ola and Quillien, V and Daver, A and Ricolleau, G and Meijer-van Gelder, E and Manders, P and Fiets, WE and Blankenstein, MA and Broet, P and Romain, S and Daxenbichler, G and Windbichler, G and Cufer, T and Borstnar, S and Kueng, W and Beex, LVAM and Klijn, JGM and O'Higgins, N and Eppenberger, U and Janicke, F and Schmitt, M and Foekens, JA},
  issn         = {1460-2105},
  language     = {eng},
  number       = {2},
  pages        = {116--128},
  publisher    = {Oxford University Press},
  series       = {Journal of the National Cancer Institute},
  title        = {Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients},
  url          = {http://dx.doi.org/10.1093/jnci/94.2.116},
  volume       = {94},
  year         = {2002},
}