Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM+ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker.
Bibliographical noteFunding Information:
The authors thank Cytogen, Inc. for assistance with cell size measurement. The authors thank Dr Juneyoung Lee in the Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea, for statistical consultation. This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Authors’ roles: Study design: SIP and SWC. Clinical data collection and interpretation: KHL, TYK, SWC and SAI. Clinical imaging study: FH, GJC and SWC. Flow cytometry and in vivo experiments: KJL, HJS, SIP and SWC. Data analysis and interpretation: SIP and SWC. Drafting manuscript: KHL, KJL, SIP and SWC. Revising manuscript: KHL, SIP and SWC. All authors approved the final manuscript.
This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040).
© 2020 American Society for Bone and Mineral Research
- BONE METASTASIS
- BREAST CANCER
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine