Abstract P6-16-01: Differences in patterns of change of bone turnover markers during treatment with bone-modifying agents of breast cancer patients with bone metastases
Authors: Higuchi T , Nishimukai A , Yanai A , Miyagawa Y , Murase K , Imamura M , Ozawa H , Takatsuka Y , Miyoshi Y 
Published: May 2016

Background: Bone-modifying agents have demonstrated their efficacy for treatment by suppressing osteoclast function. The activity of bone-modifying agents can be monitored by means of bone resorption markers such as c-terminal crosslinking telopeptide of type I collagen (1CTP) and N-telopeptide of type I collagen (NTX) as well as bone forming marker bone-specific alkaline phosphatase (BAP). In contrast to these markers which indirectly indicate bone turnover, tartrate-resistant acid phosphatase-5b (Tracp-5b) has been established as a direct marker showing osteoclast number and activity. The aim of this study was to identify the relative significance of these bone turnover markers as indicators of treatment efficacy induced by bone-modifying agents for breast cancer patients with bone metastases.

Patients and Methods: For this study, 52 breast cancer patients with bone metastases treated with bone-modifying agents were recruited. Zoledronic acid and denosumab were administered as bone-modifying agents to 36 and 22 patients, respectively (for 6 patients, denosumab was used after zoledronic acid). Serum Tracp-5b, 1CTP, NTX and BAP were measured with, respectively, the EIA (enzyme immunoassay), RIA (two-antibody radioimmunoassay), ELISA (enzyme-linked immunosorbent assay) and CLEIA (chemiluminescent enzyme immunoassay) method. Blood samples were obtained pretreatment and 1, 3 and 6 months after treatment. Changes in these bone turnover markers were statistically analyzed with Friedman's test, and correlation between serum markers and clinicopathological factors was calculated with Mann-Whitney's test.

Results: Serum tracp-5b decreased significantly after treatment (p&lt;0.0001). The baseline median value of Tracp-5b (457.5mU/dl, range: 173-1630mU/dl) had been reduced to 137mU/dl (91-795mU/dl) 1 month after treatment, but no further reduction was observed after that. For 13 out of 15 patients to whom Tracp-5b was administered, abnormally high levels (above 420mU/dl) decreased to normal range with one month treatment. Serum NTX was also significantly reduced after treatment (p=0.0007). The median baseline value (16.5nmolBCE/L, 6.1-52.2nmolBCE/L) was diminished after 1 month (to 10.9nmolBCE/L, 7.0-49.5nmolBCE/L), and further reduction of NTX was observed after 3 months (9.55nmolBCE/L, 6.4-56.0nmolBCE/L). Similarly, baseline BAP (15.1μg/L, 6.4-81.3μg/L) decreased significantly (p=0.0032), a reduction which was obtained after 3 months (10.15μg/L, 6.1-51.7μg/L), but not after 1 month (13.0μg/L, 7.7-137.0μg/L). On the other hand, reduction in 1CTP was not significant (p=0.83).

Conclusion and discussion: Although baseline values of the bone turnover markers Tracp-5b, NTX and BAP decreased significantly after treatment with bone-modifying agents, the pattern of reduction for these three markers varied. Tracp-5b appears to reflect efficacy of bone-modifying agents most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings may prove usefulness of Tracp-5b when considering the efficacy of various bone-modifying agents in clinical practice.

Citation Format: Higuchi T, Nishimukai A, Yanai A, Miyagawa Y, Murase K, Imamura M, Ozawa H, Takatsuka Y, Miyoshi Y. Differences in patterns of change of bone turnover markers during treatment with bone-modifying agents of breast cancer patients with bone metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-16-01.