C-TERMINAL TELOPEPTIDE OF TYPE I COLLAGENE – PROGNOSTIC FACTOR OF SKELETAL METASTASES IN BREAST CANCER PATIENTS

N.V. Lyubimova1, G.V. Kozharskaya2, Yu.S. Timofeev1, S.M. Portnoy1
1N.N.Blokhin Russian Cancer Research Center RAMS, Kashirskoe shosse, 24, Moscow, Russian Federation, 115478;
2Oncologic Dispensary № 5, Perervinsky Boulevard, 5/1, Moscow, Russian Federation, 109451

Introduction. Skeletal involvement is a frequent and troublesome complication of breast malignant tumors. The accurate diagnosis of bone metastasis and well-timed prescription of the antiresorptive therapy are essential for reducing both severity and mortality. Recently different markers of bone turnover are using in diagnosis and monitoring therapeutic response in cancer patients with metastatic bone disease. The predictive value of bone resorption and formation markers in breast cancer patients is of great interest for the optimization of application of bisphosphonates The aim of the study. The analysis of associations between serum C-terminal telopeptide of type I collagen (СТX) as bone resorption and activity of bone-specific alkaline phosphatase (BAP) as formation marker, with survival of breast cancer patients monitored for 6 years were evaluated to reveal their clinical implications. Methods. Serial measures of CTX and BAP in blood serum of 72 breast cancer patient with bone metastasis and 167 – without bone involvement have been done with the use of ELISA test-systems «Serum CrossLaps» (Osteometer) и «Metra BAP» (Quidel Cor.). Control group included 47 healthy females.Results. Elevated rate of bone turnover correlated with high levels of CTX and BAP and was associated with reduced overall survival of breast cancer patients. The significant differences of overall survivability of patients with values higher than cut-off of CTX (0,74 ng/ml) and BAP (43,7 IU/L) if compared to those with normal levels were found in all groups of patients. CTX was superior to BAP as predictor of outcome in breast cancer patients with bone metastases. Multivariate Cox proportional hazards regression analysis revealed that CTX was independent prognostic factor for breast carcinoma related death together with some clinical pathological characteristics (tumor malignancy). Conclusion. Serum СТх and BAP are of value in predicting the status of breast cancer bone metastases and optimization of bisphosphonates therapy. CTX was shown to be independent prognostic factor of bone involvement.
Keywords: 
C-telopeptide of type I collagen, bone alkaline phosphatase, breast cancer, bone metastases, prognosis