Breast-conserving therapy: proteases as risk factors in relation to survival after local relapse

J Clin Oncol. 1999 May;17(5):1449-57. doi: 10.1200/JCO.1999.17.5.1449.

Abstract

Purpose: To evaluate whether cathepsin D, urokinase-type plasminogen activator (uPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence (LR).

Patients and methods: Of 1,630 patients treated with breast-conserving surgery and radiotherapy of the breast between 1980 and 1992, LR developed in 171 as a first event. From the available primary tumor tissues, we determined the cytosolic levels of cathepsin D, uPA and PAI-1.

Results: In patients with LR, a short (< or = 2 years) disease-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P = .001, both) and postrelapse overall survival (PR-OS; P < .0001 and P < .0002, respectively). The primary tumor levels of uPA and PAI-1 were elevated for patients with a short DFI (P < .01), but such a relation was not observed for patients with skin involvement. In univariate analyses, high levels of uPA and PAI-1 in the primary tumor were associated with poor PR-OS (P = .038 and P = .040, respectively) but not PR-DMFS. In Cox multivariate analyses for PR-DMFS and PR-OS, only a short DFI and skin involvement of the LR were independently associated with a poor clinical outcome.

Conclusion: In patients treated with breast-conserving therapy who had LR as a first event, a short DFI and skin involvement were strong indicators for poor PR-DMFS and PR-OS. The proteases studied did not contribute significantly to the final multivariate model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cathepsin D / analysis*
  • Cytosol / chemistry
  • Disease-Free Survival
  • Female
  • Humans
  • Mastectomy, Segmental
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Recurrence, Local
  • Plasminogen Activator Inhibitor 1 / analysis*
  • Proportional Hazards Models
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Risk Factors
  • Urokinase-Type Plasminogen Activator / analysis*

Substances

  • Neoplasm Proteins
  • Plasminogen Activator Inhibitor 1
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Urokinase-Type Plasminogen Activator
  • Cathepsin D