Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following first relapse

Breast Cancer Res Treat. 1999 Mar;54(2):147-57. doi: 10.1023/a:1006118828278.


In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI-1) in primary breast cancer. The prognostic impact of invasion markers PAI-1 and urokinase-type plasminogen activator (uPA) on disease-free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI-1 and uPA after long-term median follow-up of 77 months for our cohort (n = 316). Levels of uPA, PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S-phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log-rank statistics, optimized cutoffs were found for PAI-1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI-1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p < 0.001, RR: 3.1) and PAI-1 (p < 0.001, RR: 2.7) remained significant. In node-negative patients (n = 147), PAI-1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI-1 was significant. PAI-1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAT-1 and nodal status for determination of a very-low-risk subgroup. For OS, only lymph node status and PAI-1 were significant in multivariate analysis. PAI-1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Cathepsin D / analysis
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Plasminogen Activator Inhibitor 1 / analysis*
  • Ploidies
  • Prognosis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • S Phase
  • Survival Analysis
  • Time Factors
  • Urokinase-Type Plasminogen Activator / analysis*


  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Urokinase-Type Plasminogen Activator
  • Cathepsin D