Abstract P2-08-24: High levels of serum C-terminal crosslinking telopeptide of type 1 collagen at baseline are associated with poor prognosis for breast cancer patients
Authors: Imamura M , Nishimikai A , Yanai A , Miyagawa Y , Higuchi T , Ozawa H , Murase K , Takatsuka Y , Miyoshi Y 
Published: May 2016

Abstract
Background: It has been demonstrated that adjuvant treatment using bisphosphonate may reduce recurrence among breast cancer patients. However, these improved prognoses of patients are reportedly limited to breast cancers of estrogen receptor (ER)-positive and postmenopausal women. Although the mechanisms of the effects of bisphosphonate remain unknown, this finding seems to represent support for the hypothesis that suppression of bone resorption by bisphosphonate results in favorable prognoses at least for patients in this subset. In order to determine the prognostic significance of bone resorption in breast cancer patients, we investigated these markers c-terminal crosslinking telopeptide of type I collagen (1CTP) and N-telopeptide of type I collagen (NTX).
Patients and Methods: 469 breast cancer patients were recruited who were operated on Hyogo College of Medicine and histologically confirmed to have invasive carcinoma. Serum 1CTP and NTX were measured preoperatively with the two-antibody radioimmunoassay and enzyme-linked immunosorbent assay methods, respectively, and blood samples were obtained before treatment from patients who were treated with neoadjuvant chemotherapy or endocrine therapy. The area under receiver operating characteristic curves were applied and optimal cutoff values were set at 3.6ng/ml for 1CTP, and 10.55nmolBCE/L premenopausal and 14.05nmolBCE/L postmenopausal for NTX. The relationships between these bone turnover markers and various clinicopathological characteristics were evaluated with the chi square or Fisher's exact test. The log-rank test was used to compare relapse-free survival (RFS) in Kaplan-Meier plots. Associations of RFS were assessed with a Cox proportional-hazards model based on the results of univariate and multivariate analyses. Differences were considered statistically significant if p&lt;0.05.
Results: There were significantly more 1CTP-high patients among postmenopausal women and RFS of 1CTP-high patients was significantly worse than that of 1CTP-low patients (5-year RFS: 0.65 vs 0.86; p=0.0002). Similarly, NTX-high patients were significantly associated with postmenopausal status, but there was no significant association between NTX-high worse RFS (p=0.0976). Multivariate analysis of tumor size, lymph node metastasis and nuclear grade identified 1CTP (hazard ratio: 2.04, 95% confidence interval: 1.13-3.68; p=0.018) as a significant independent prognostic factor. Subset analyses of 1CTP showed that prognosis was consistently worse recognized for postmenopausal (p=0.0002), but not premenopausal (p=0.37) patients. Furthermore, prognosis for 1CTP-high patients was worse for the estrogen receptor (ER)-positive subset (p=0.0005) but not for the ER-negative subset (p=0.22).
Conclusion and discussion: High levels of serum bone resorption markers at baseline were identified as significant unfavorable prognostic factors for breast cancer patients. The prognostic significance of 1CTP seems to be prominent for postmenopausal patients with ER-positive breast cancers. These findings suggest the use of bone-modifying agents as an adjuvant therapy may be beneficial for breast cancer patients, especially for patients with high serum levels of 1CTP.
Citation Format: Imamura M, Nishimikai A, Yanai A, Miyagawa Y, Higuchi T, Ozawa H, Murase K, Takatsuka Y, Miyoshi Y. High levels of serum C-terminal crosslinking telopeptide of type 1 collagen at baseline are associated with poor prognosis for breast cancer patients. [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 P2-08-24.