Prognostic impact of proteolytic factors (Urokinase-Type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy

Citation
N. Harbeck et al., Prognostic impact of proteolytic factors (Urokinase-Type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy, CLIN CANC R, 7(9), 2001, pp. 2757-2764
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2757 - 2764
Database
ISI
SICI code
1078-0432(200109)7:9<2757:PIOPF(>2.0.ZU;2-5
Abstract
Purpose: Prognostic and predictive impact of five proteolytic factors assoc iated with tumor invasion and metastasis in primary breast cancer were eval uated after longterm follow-up. Experimental Design: Antigen levels of urokinase-type plasminogen activator , plasminogen activator inhibitor-1 (PAI-1), Cathepsins B, D, and L were de termined using immunochemical assays in primary tumor tissue of 276 patient s. Results: During follow-up (median 109 months), 119 (43%) patients relapsed, and 117 (42%) died. In the whole collective, 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) we re the only independent significant factors in multivariate analysis for di sease-free survival (DFS). For overall survival (OS), lymph node status (P < 0.001; RR 2.9), Cathepsin L (P = 0.017; RR 1.9), PAI-1 (P = 0.01; RR 1.9) , and grading (P = 0.026; RR 1.7) were significant. In the node-negative su bgroup, PAI-1 was the only significant factor for DFS (P = 0.004; RR 3.7) a nd the strongest factor (P = 0.004; RR 3.7) for OS next to grading (P = 0.0 17; RR 3.1). In nodepositive patients, Cathepsin L was the only significant factor for both DFS (P < 0.001; RR 3.2) and OS (P = 0.003; RR 2.5). For al l proteolytic factors but Cathepsin L, the univariate prognostic impact on DFS was substantial in patients without adjuvant systemic therapy but was d iminished if adjuvant therapy had been administered. Cathepsin L maintained its strong prognostic impact on DFS even in patients with adjuvant endocri ne therapy (P = 0.01; RR 2.8). Conclusions: The observed effect of adjuvant systemic therapy on their prog nostic strength suggests that the assessed proteolytic factors supply predi ctive information on therapy response.