Abstract P2-19-02: Circulating osteocalcin-positive cells as a novel diagnostic biomarker for bone metastasis in breast cancer patients

Abstract

Abstract Purpose: Diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone. We investigated whether circulating osteocalcin-positivecells (cOC) could detect the incipient and/or progressive BM earlier than image-based diagnostics. Experimental design: Metastatic breast cancer patients with or without bone metastasis (designated BM+ or BM-) were enrolled and cOC were quantified at baseline by flow cytometry. The progression of BM was evaluated after 18 months. Murine BM models were established by intra-tibial or -cardiac injection of MDA-MB-231 or 4T1 breast cancer cells. Results: In the baseline analysis, cOC was significantly higher in BM+ than BM- group. In the 18-month follow-up study of BM+ patients (n=63), baseline cOC was significantly associated with BM disease progression. Among BM- patients (n=33), three patients developed new bone metastasis within 18 months and were found to have had higher cOC at baseline. The patients with higher cOC showed shortened BM progression-free survival, compared with those with lower cOC (cutoff=0.045%; P<.001; HR 4.79; 95% CI 2.17-10.56). In murine intra-tibial injection models, cOC significantly increased at an early time-point, even when micro-metastases were evident only by histologic examination but undetectable by bioluminescence imaging. Additionally, in an intra-cardiac injection model, the mice with higher cOC developed BM at an earlier time point, compared with the mice with lower cOC. Conclusions: cOC is increased in the early phase of breast cancer BM and predict the disease progression. cOC can be a novel biomarker for early diagnosis and progression of BM. Citation Format: Sun Wook W Cho, Kyung-Hun Lee, Tae-Yong Kim, Serk In Park, Seock-Ah Im. Circulating osteocalcin-positive cells as a novel diagnostic biomarker for bone metastasis in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-19-02.