26P - Circulating osteocalcin-positive cells, as a novel biomarker for monitoring the therapeutic effects on bone metastasis

Background

Imaging-based assessment for tumor progression in bone metastasis is difficult because of the nature of fixed bony defects and their complexity. The aime of this study was to investigate the circulating osteocalcin-positivecells (cOC) in the peripheral blood as a biomarker for monitoring the therapeutic effects on bone metastasis.

Methods

An animal model of bone metastasis was established by intratibial injection of MDA-MB-231-luc cells into nude mice and treated with zolendronate (ZA) for 4 weeks. cOC was characterized as CD15^-CD45^-Osteocalcin⁺ cell fractions from the peripheral blood mononuclear cells using a flow cytometry. Breast cancer patients treated with ZA for bone metastasis were recruited, and cOC was measured.

Results

In animal model, ZA significantly reduced % tumor area and TRAP+ osteoclasts in histological analysis and tumor growth in bioluminescence images from 2-3 weeks after treatment. Serum TRAP5b or C-terminal telopeptide (CTx) levels were significantly decreased from 2 weeks in ZA-treated group. Earlier than these, cOC in peripheral blood was significantly decreased from 1 weeks after treatment. In patients with bone metastasis, the decrease in cOC was significantly frequent in the ZA-responsive group than in the ZA-nonresponsive group, whereas the serum CTx levels did not differ between the groups.

Conclusions

cOC can predict therapeutic response in bone metastasis of breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Sun Wook Cho.

Funding

Cellus, Inc.

Disclosure

M.J. Kim: Financial Interests, Personal, Full or part-time Employment: Cellus, Inc. S.W. Cho: Financial Interests, Personal, Officer: Cellus, Inc. All other authors have declared no conflicts of interest.