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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yamashita
J
J
Department of Surgery II, Fukuoka University Medical School, Japan.
Ogawa
M
M
Sakai
K
K
D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D016232:Endothelins / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019272:Leukocyte Elastase; D015411:Mastectomy, Modified Radical; D015409:Mastectomy, Radical; D009367:Neoplasm Staging; D010196:Pancreatic Elastase / Q000032:analysis*; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D016232:Endothelins; D013629:Tamoxifen; D010741:Phospholipases A; D054467:Phospholipases A2; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator