Abstract P5-09-05: Prediction of bone metastases of breast cancer using combined markers of bone metabolism and inflammation
Authors: Nishimukai Arisa , Shibata Naoya , Kikuchi Wataru , Hutawatari Hiroki , Ishihara Hideki , Miyoshi Yasuo 
Published: May 2015

Abstract
Introduction
Bone metastases in breast cancer impair a patient's QOL because of skeletal-related events such as bone pain, fractures, spinal cord compression, and hypercalcemia. It might be important to predict bone metastases and initiate adequate treatment early in the disease process. Screening and diagnosis of bone metastases are performed using serum markers and imaging systems such as CT, MRI, PET, and SPECT in postoperative testing. However, a method for predicting bone metastases for stratifying patients who require treatment has not been established. Although various markers of bone metabolism have been approved for monitoring of postoperative bone metastases, these are not considered clinically practical because of their low specificity. We selected TRACP-5b as a marker of bone metabolism; likelihood of bone metastases, and CRP as a marker of inflammation; likelihood of distant recurrence. We hypothesized that the combination of these two markers of different aspects would provide an accurate prediction of bone recurrence.
Patients and methods
Three hundred forty-nine breast cancer patients who underwent surgery in our hospital between August 5, 2010, and October 31, 2013, were enrolled in this study. Their serum levels of TRACP-5b and CRP were measured in a blinded manner at the R & D laboratory of Nittobo Medical Co., Ltd. Eighty-one patients were excluded (78 cases; neoadjubant chemotherapy administration, 3 cases; T4), and the data from the remaining 268 patients were included in the statistical analysis. The cutoff values were 380mU/dL for TRACP-5b and 0.016 mg/dL for CRP. Patients with both values above the cutoff value were classified as +/+, and they were compared with the other patients. The odds ratio between +/+ and the others were calculated using MedCalc statistical software.
Results
Patients stratified into four classes according to the value of TRACP-5b and CRP: +/+ (n=60), +/- (n=49), -/+ (n=76) and -/- (n=83), (+ means above the cutoff value). Eight of the 268 patients had relapsed metastases: three in the bone only, one in the bone and lung, three in lymph nodes only, and one in the lung only). The Incidence of bone metastases was 5 %(3/60) in the +/+ patients and 0.5 %(1/208) in the others. The incidence was significantly higher in the +/+ patients than in the others(odds ratio: 10.9, 95% CI 1.11 to 106.74, p= 0.040). When the other relapses not including bone metastases were included in the analysis, no significant difference was observed between the two groups (odds ratio: 0.4, 95% CI 0.02 to 7.07, P=0.513). TRACP-5b concentration alone could not classify the patients into two groups according to significantly different incidences of bone metastases(odds ratio: 4.5, 95% CI 0.46 to 43.57, P=0.197).
Conclusion
The results presented here show that the prediction of bone metastases by the combination of TRACP-5b and CRP concentrations is clinically relevant. We plan to increase the number of patients to provide sufficient statistical power to confirm this diagnostic potential.
Citation Format: Arisa Nishimukai, Naoya Shibata, Wataru Kikuchi, Hiroki Hutawatari, Hideki Ishihara, Yasuo Miyoshi. Prediction of bone metastases of breast cancer using combined markers of bone metabolism and inflammation [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-09-05.