Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study

Abstract

Background: Serum bone turnover markers might play a role in the prediction of the development of bone metastases in breast cancer (BC) patients. We conducted a retrospective cohort study to address the association of serum bone turnover markers with oncologic outcomes. Methods: We included 80 women with BC, who were operated on at the Department of Gynecology, Obstetrics and Reproductive Medicine, Homburg/Saar, Germany. Serum samples were obtained prior to surgery and were used for estimation of the concentration of tumor and bone turnover markers using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Results: At baseline, pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen (ICTP) concentrations were higher in nodal positive vs. negative tumors (Mann–Whitney test p = 0.04). After a median follow-up of 79.4 months, 17 patients developed metastases, with 9 demonstrating, among other organs, osseous metastases. ICTP demonstrated the best area under the curve in the predection of osseous metastases in our cohort (AUC = 0.740, DeLong Test p = 0.005). Univariable Cox proportional hazard models failed to demonstrate significant associations between serum bone turnover markers and oncologic outcomes (progression-free survival, overall survival). Conclusions: Serum bone turnover markers (e.g., ICTP) were able to predict the development of osseous metastases but were not associated with oncologic outcomes. Further investigation and validation are required for the use of such markers in clinical practice.