Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases

Breast Cancer. 2020 Nov;27(6):1065-1071. doi: 10.1007/s12282-020-01109-9. Epub 2020 May 15.

Abstract

Background: Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab.

Methods: Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1 month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis.

Results: Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0 months; high group 54.0 months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028).

Conclusion: We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.

Keywords: Bone metastasis; Breast cancer; Denosumab; Prognostic indicator; Urinary N-telopeptide of type I collagen (u-NTX).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Biomarkers, Tumor / urine*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / mortality*
  • Bone Neoplasms / secondary
  • Bone Neoplasms / urine
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / urine
  • Collagen Type I / urine*
  • Denosumab / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Middle Aged
  • Peptides / urine*
  • Radionuclide Imaging
  • Retrospective Studies
  • Risk Assessment / methods

Substances

  • Biomarkers, Tumor
  • Bone Density Conservation Agents
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Denosumab