Diagnostic and prognostic value of serum nitric oxide, tumor necrosis factor-alpha, basic fibroblast growth factor and copper as angiogenic markers in premenopausal breast cancer patients: a case-control study

Many studies demonstrate that increased microvessel density (MVD) surrounding primary tumour is associated with decreased overall survival in patients with breast cancer. This study compares the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumour necrosis factor-a (TNF alpha), basic fibroblast growth factor (bFGF) and copper with those of serum CA15-3 as the standard tumour marker in breast cancer patients. Microvessel density was estimated in CD31-immunostained sections from breast cancer patients. Before surgery, NO, TNF alpha, bFGF, copper and CA 15-3 were measured in serum samples from 30 premenopausal breast cancer patients in comparison with 15 healthy controls. The diagnostic values of the assayed parameters were compared using receiver operating characteristic (ROC) curve analysis. Univariate survival analysis of patients was assessed using the Kaplan-Meier method. Breast cancer tissues showed higher MVD than did normal breast tissues adjacent to the tumour (P=0.008). Before surgery, tumour MVD correlated significantly with serum NO, TNF alpha, bFGF and copper (r=0.458, P=.011; r=0.379, P=.039; r=0.513, P=.004 and r=0.613, P=0.000, respectively). Serum NO, TNF alpha, bFGF, copper and CA 15-3 levels in patients were significantly elevated compared with controls (P=0.011, P=0.004, P=0.039, P=0.000 and P=0.001, respectively). Kaplan-Meier analysis revealed that patients with elevated serum TNE alpha, CA 15-3 and copper (P=0.035, P=0.040, P=0.0339, respectively) had an overall survival significantly shorter than those who had lower levels of these parameters. These data suggest that serum TNF alpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.