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

Purpose: To evaluate whether cathepsin D, urokinase-type plasminogen activa tor (UPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or cli nical 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 surg ery and radiotherapy of the breast between 1980 and 1992, LR developed in 1 71 as a first event. From the available primary tumor tissues, we determine d the cytosolic levels of cathepsin D, uPA and PAI-1. Results: In patients with LR, a short (less than or equal to 2 years) disea se-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P =.001,both) and p ostrelapse overall survival (PR-OS; P <.0001 and P <.0002, respectively). T he 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 t he primary tumor were associated with poor PR-OS (P =.038 and P =.040, resp ectively) but nat PR-DMFS, In Cox multivariate analyses for PR-DMFS and PR- OS, only a short DFI and skin involvement of the LR were independently asso ciated with a poor clinical outcome. Conclusion: In patients treated with breast-conserving therapy who had LR a s a first event, a short DFI and skin involvement were strong indicators fo r poor PR-DMFS and PR-OS. The proteases studied did not contribute signific antly to the final multivariate model. J Clin Oncol 17:1449-1457, (C) 1999 by American Society of Clinical Oncology.