Neopterin Is an Independent Prognostic Variable in Females with Breast Cancer

Abstract

BACKGROUND: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-gamma, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in neopterin in the serum and urine of patients depends on tumor stage and type. METHODS: In a retrospective study comprising 129 females with breast cancer, urinary neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. RESULTS: Urinary neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases (P <0.05) and by tumor differentiation (P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases (P <0.001), neopterin (P <0.001), tumor size (P = 0.001), and lymph node status (P <0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases (P <0. 001), neopterin (P <0.01), and lymph node status (P <0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased neopterin concentrations was 2.5 compared with patients with neopterin concentrations within the reference interval. CONCLUSION: Urinary neopterin provides additional prognostic information in patients with breast cancer.