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-alpha (TNFalpha), 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, TNFalpha, 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, TNFalpha, 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, TNFalpha, 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 TNFalpha, 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 TNFalpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.
Serum sFas and p53 protein have been observed in breast cancer patients, but their clinical usefulness for diagnosis and therapy monitoring has not been clarified. The aim of this study was to compare the clinical utility of serum sFas and p53 protein with that of serum CA 15-3 as the most commonly used breast cancer tumor marker. Serum samples were taken from 35 normal healthy controls and 35 breast cancer patients before surgery, after 2 weeks of surgery and after six cycles of FAC chemotherapy. Serum sFas and p53 protein levels were measured using ELISA kits. Serum CA 15-3 levels were determined using IRMA kit. Mean Serum levels of sFas and CA 15-3 were significantly elevated while p53 protein was significantly declined in breast cancer patients than controls. Serum p53 protein showed the greatest significant area under the ROC curve (84.3%) followed by sFas (80.5%), then CA 15-3 (78%). The sensitivity, specificity and cut-off value for diagnosing breast cancer patients were 84.2%, 82.6% and 2.88 U/ml for p53 protein, 83.3%, 68.2% and 497.3 pg/ml for sFas and 45.8%, 100% and 23 U/ml for CA15-3. Surgical removal of breast resulted in a significant decline in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. Six cycles of chemotherapy resulted in a significant elevation in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. sFas was significantly correlated with tumor grade. It could be concluded that although serum p53 protein is superior to sFas and CA15-3 for diagnosis of breast cancer patients, only sFas is useful for monitoring the response of breast cancer patients to surgery and chemotherapy if the effect of systemic inflammatory reactions is excluded.
Aim: To investigate the influence of the polymorphic variants of CCND1 (G870A) and p73 (G4C14-to-A4T14) on the susceptibility to breast cancer development, also, to figure out their diagnostic and prognostic roles. Subjects and Methods: Blood samples were obtained from breast cancer patients and controls. Genotyping of CCND1 and p73 genes were carried out by PCR-RFLP and PCR-CTPP; respectively. Results: In comparison with the control group, CCND1 (G870A) GA and AA genotypes frequencies were significantly higher in breast cancer patients (p=0.035 and p=0.002; respectively), whereas CCND1 (G870A) GG genotype frequency was significantly lower (p< 0.001). The CCND1 GA and AA genotypes significantly increased the risk for developing breast cancer compared with the GG genotype. The CCND1 (GA+AA) genotypes were significantly correlated with disease-free survival (DFS) of breast cancer patients. In comparison with the control group, p73 (G4C14/A4T14) GC/AT and AT/AT genotypes frequencies were significantly higher in breast cancer patients (p=0.013 and p=0.04; respectively), whereas p73 (G4C14/A4T14) GC/GC genotype frequency was significantly lower (p= 0.004). Compared with the GC/GC genotype, the p73 GC/AT and AT/AT genotypes significantly increased the risk for developing breast cancer. Beside being significantly correlated with DFS, p73 [(GC/AT)+ (AT/AT)] genotypes were indirectly correlated with tumor size, tumor pathological grade, patient's clinical stage, number of axillary lymph node involvement and Her2/neu expression. Conclusion: The GA and AA genotypes of CCND1 (G870A) polymorphism and the GC/AT and AT/AT genotypes of p73 (G4C14-to-A4T14) polymorphism can be used as diagnostic markers in breast cancer patients. The presence of the CCND1 (G870A) GA and AA genotypes and the GC/AT and AT/AT genotypes of p73 (G4C14-to-A4T14) polymorphism can increase the susceptibility to breast cancer incidence. Both of CCND1 (G870A) and p73 (G4C14-to-A4T14) polymorphisms can be used for prognosis of breast cancer patients.
Aim: To evaluate the diagnostic and prognostic value of serum 25-hydroxyvitamin D (25(OH) D), ionized calcium and phosphorus in comparison with serum CA15.3 as the most commonly used breast cancer marker. Participants and methods: This study was conducted on 45 breast cancer female patients with recently detected breast cancer before surgery and 45 apparently healthy female controls of matched age, menstrual and socioeconomic status as breast cancer patients group. Serum 25(OH) D, ionized calcium, phosphorus and CA15.3 were measured using readyfor-use commercially available kits. Results: Serum levels of 25(OH) D and ionized calcium in the breast cancer patients group were significantly lower than those of the control group, while serum levels of phosphorus and CA15.3 in breast cancer patients group were significantly higher than those of the control group. The area under the ROC curve for serum ionized calcium (81.7%) was significantly greater than that of 25(OH) D (75.3%), CA 15.3 (70.1%) and phosphorus (62.8%). The odd's ratio of vitamin D was 0.0937 (95% CI=0.0311-0.2823), of ionized calcium was 0.0464 (95% CI=0.015-0.141) and of phosphorus was 2.6801(95% CI=1.1269-6.3742) in breast cancer patients group. Serum phosphorus was significantly correlated with age and menopausal status of breast cancer patients. Conclusion: Our results suggest that serum ionized calcium and 25(OH) D were superior to serum CA15.3 and phosphorus for prediction of breast cancer. In addition, our results indicate that 25 (OH) D and calcium may decrease the risk for breast cancer incidence, while phosphorus may increase this risk. None of the assayed biomarkers has a prognostic role in breast cancer.
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