Breast-Conserving Therapy: Proteases as Risk Factors in Relation to Survival After Local Relapse

• Published in: Journal of clinical oncology Vol. 17; no. 5; pp. 1449 - 1457
• Main Authors: GELDER, M. E. M.-V, LOOK, M. P, VRIES, J. B.-D, PETERS, H. A, KLIJN, J. G. M, FOEKENS, J. A
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.05.1999; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biological and medical sciences; Breast Neoplasms - chemistry; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cathepsin D - analysis; Cytosol - chemistry; Disease-Free Survival; Female; Humans; Mastectomy, Segmental; Medical sciences; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Recurrence, Local; Plasminogen Activator Inhibitor 1 - analysis; Proportional Hazards Models; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Risk Factors; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the genital tract and mammary gland; Urokinase-Type Plasminogen Activator - analysis; Relapse; u-Plasminogen activator; Prognosis; Estrogen; Metastasis; Premises; Plasminogen activator inhibitor 1; Conservative surgery; Aspartic endopeptidases; Cathepsin D; Mammary gland; Biological receptor; Human; Serine endopeptidases; Enzyme; Malignant tumor; Ovarian hormone; Mammary gland diseases; Peptidases; Treatment; Risk factor; Hydrolases; Progesterone; Sex steroid hormone; Hormonal receptor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.1999.17.5.1449

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). 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. 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. 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.