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High levels at baseline of serum pyridinoline crosslinked carboxyterminal telopeptide of type I collagen are associated with worse prognosis for breast cancer patients

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Abstract

It is speculated that adjuvant use of bisphosphonate reduces recurrence in breast cancer patients through suppression of bone resorption. To determine the prognostic impact of bone resorption markers, we investigated serum levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (1CTP) and N-terminal crosslinking telopeptides of type I collagen (NTX). 1CTP and NTX were measured at baseline (before operation or neoadjuvant therapies) and afterward in 469 patients operated on breast cancer. The optimal cutoff value of 1CTP for relapse-free survival (RFS) was set at 3.6 ng/ml with an area under the receiver operating characteristics curve of 0.641 [95 % confidence interval (CI) = 0.560–0.721; p = 0.0011]. However, we were unable to determine a significant cutoff value for NTX. RFS was significantly worse for 1CTP-high patients with than for those with low levels of 1CTP (p = 0.0002). Multivariate analysis with tumor size, lymph node metastasis, and nuclear grade showed that 1CTP was a significant independent prognostic factor (hazard ratio = 2.04, 95 % CI = 1.13–3.68; p = 0.018). Worse prognosis for the subset with high 1CTP levels applied only to postmenopausal patients (p = 0.0002). RFS of 130 patients whose 1CTP changed from low at baseline to high at 6 months postoperatively showed RFS almost as poor as that for patients with high 1CTP throughout. These findings suggest that 1CTP may be useful not only for identifying patients with unfavorable prognosis, but also for selecting patients who may benefit from administration of bone-modifying agents in an adjuvant setting.

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Acknowledgments

The present study was supported by the grant of Hyogo College of Medicine.

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Authors and Affiliations

  1. Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan

    Michiko Imamura, Arisa Nishimukai, Tomoko Higuchi, Hiromi Ozawa, Ayako Yanai, Yoshimasa Miyagawa, Keiko Murase, Yuichi Takatsuka & Yasuo Miyoshi

  2. Sakita Clinic, Nishinomiya, Hyogo, Japan

    Isao Sakita

  3. Uminosato Clinic, Minamiawaji, Hyogo, Japan

    Takuya Hatada

  4. Division of Genome Medicine, Institute for Genome Research, University of Tokushima, Tokushima, Tokushima, Japan

    Toyomasa Katagiri

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  1. Michiko Imamura
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Correspondence to Yasuo Miyoshi.

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10549_2015_3638_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 74 kb). (Supplemental figure) Receiver operating characteristics (ROC) curves for 1CTP and NTX for relapse-free survival. The cutoff values were set at 3.6 ng/ml for 1CTP and 14.05 nmol BCE/L for NTX with the areas under the curves (AUC), that is, 0.641 (95 % confidence interval (CI) = 0.560-0.721, p = 0.0011) for 1CTP and 0.549 (95 % CI = 0.461-0.637, p = 0.27) for NTX

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Imamura, M., Nishimukai, A., Higuchi, T. et al. High levels at baseline of serum pyridinoline crosslinked carboxyterminal telopeptide of type I collagen are associated with worse prognosis for breast cancer patients. Breast Cancer Res Treat 154, 521–531 (2015). https://doi.org/10.1007/s10549-015-3638-2

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