Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: Results from a 2-year multicentre observational study (ZOMAR study)

Agustí Barnadas, Luis Manso, Concepción de la Piedra, Cristina Meseguer, Carmen Crespo, Patricia Gómez, Lourdes Calvo, Purificación Martinez, Manuel Ruiz-Borrego, Antonia Perelló, Antonio Antón, Manuel Codes, Mireia Margelí, Adolfo Murias, Javier Salvador, Miguel Ángel Seguí, Ana de Juan, Joaquín Gavilá, María Luque, Diego PérezPilar Zamora, Alberto Arizcuma, José Ignacio Chacón, Lucía Heras, Marta Martin-Fernández, Ignacio Mahillo-Fernández, Ignacio Tusquets

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15 Citations (Scopus)

Abstract

Background: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. Methods: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4 mg every 28. days) from the baseline visit. Results: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3 months ( P< 0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P = 0.0259]) and at 3. months (3.41 [95% CI: 1.367-8.498; P = 0.0085]). HRs > 2 were found for increased baseline and 3-month levels of NTX and CTC ( P< 0.05). Only increased baseline BSAP levels were associated with DP (HR = 2.25 [95% CI: 1.391-3.626; P = 0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3. months of NTX and BSAP were significantly associated with mortality (HRs = 3.59 [95% CI: 1.375-9.382; P = 0.0091] and 3.25 [95% CI: 1.293-8.189; P = 0.0120], respectively). CTC and BSAP were correlated during all study timepoints ( P< 0.05). Conclusions: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value. © 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)32-40
JournalBone
Volume68
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Bisphosphonates
  • Bone metastases
  • Bone turnover markers
  • Breast cancer
  • Circulating tumor cells
  • Zoledronic acid

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