Prognostic significance of three novel biologic factors in a clinical trial of adjuvant therapy for node-negative breast cancer

Abstract

Five products of human breast carcinoma cells, including membrane-associated phospholipase A2 (M-PLA2), polymorphonuclear leukocyte elastase (PMN-E), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and endothelin-1 (ET-1), have been implicated in the processes of tumor cell invasion and metastasis in human breast carcinoma. However, the prognostic significance of these factors has not been assessed previously in node-negative breast carcinoma, in which adjuvant treatment is dependent on risk stratification. The five products of breast carcinoma cells were measured in 184 patients with node-negative breast carcinoma who were enrolled in the Kumamoto Adjuvant Chemo-Endocrine Therapy for Breast Cancer prospective randomized trial, and the predictive values of these factors for relapse-free and overall survival were evaluated. M-PLA2, PMN-E, and t-PA were found to be significant independent predictors of relapse-free and overall survival, whereas u-PA and ET-1 were not independently predictive. Further statistical analyses showed that the predictive powers of M-PLA2, PMN-E, and t-PA were additive. A combination of these three factors identified a group of patients (approximately 50% of those who manifested node-negative breast carcinoma) with a favorable prognosis, regardless of the administration of adjuvant therapy. This study identified three biologic factors that are valuable predictors of survival in node-negative breast carcinoma. A combination of these biologic factors may allow identification of low-risk patients who could be spared adjuvant therapy.