Abstract P2-01-06: Association between Circulating Tumor Cells and Bone Turnover Markers in patients with breast cancer and bone metastases on treatment with bisphosphonates (ZOMAR study)
Authors: Manso L , Barnadas A , Tusquets I , Crespo C , Gómez P , Calvo L , Ruiz M , Martínez P , Perelló A , Antón A , Codes M , Margelí M , Murias A , Salvador J , Seguí MA , De Juán A , Gavilá J , Luque M , Pérez D , Zamora P , Arizcum A , Chacón JI , Heras L , De la Piedra C 
Published: August 2014

Abstract
Background: Quantification of Circulating Tumor Cells (CTC) has demonstrated an important role in assessing disease progression and outcomes, and pathological CTC levels are an independent prognostic factor of disease progression. High CTC levels may be associated with bone turnover markers (BTM) levels and have also been associated with the risk of skeletal-related events (SREs), disease progression and death. The aim of this study was to determine the relation between CTC, BTM, and SREs, disease progression and death in patients in patients with breast cancer (BC) and bone metastasis (BMe) treated with zoledronic Acid.
Patients and methods: Observational, prospective and multicenter study. Patients with BC and BMe; no previous bone treatment in the last 6 months prior to study entry. CTC (fluorescently labelled with nucleic acid dye 4,6-diamidino-2-phenylindole DAPI, monoclonal antibodies specific for leukocytes CD45-allophycocyanin and epithelial cells cytokeratin 8,18,19–phycoerythrin; Cell Search System Veridex); urinary aminoterminal telopeptide of collagen I (NTX, Osteomark NTx Urine, Wampole Laboratories, USA); urinary alpha-alpha-isomer of carboxyterminal telopeptide of collagen I (αα-CTX, ALPHA Crosslaps EIA, ids, UK) and serum bone alkaline phosphatase (BALP, OSTASE BAP, ids, UK) were determined at baseline (V0) and every 3 mo along 18 months (V6). Patients were treated with zoledronic acid (ZA) at inclusion and every 3–4 weeks.
Results: 234 patients with BC and BMe were analyzed, being available CTC results for 114 patients and BTM results for 219 patients at basal visit (V0) and every 3 mo of treatment along 18 months (V6). Population basal characteristics (234 patients): mean age: 59.8 years; ER+: 80.3%; PR+: 64.9%; HER 2+: 18.3%. 55.3% of patients (n = 114) had detectable CTC (CTC≥1) at V0, and 32.5% of them presented pathological (CTC≥5) at V0. A significant decrease was observed at V1, with 39.8% of patients with detectable CTC levels and 14.0% of patients with pathologic CTC levels (p &lt; 0.05). Normalized levels remained steady throughout 18 mo follow-up, finding significant decrease at V3, V4 and V5 for detectable CTC levels and at V2 for pathologic CTC levels (p &lt; 0.05). A positive correlation was observed between CTC with BTM (p &lt; 0.05) at the end of the study (V6). Regarding association between CTC and SREs, progression and exitus, respectively, a significantly greater proportion of patients with pathologic CTC levels was found among those patients presenting progression (at V6) and death (at V1, V2, V3 and V4).
Conclusion: Over 30% of mBC patients presented pathological levels of CTC. Addition of ZA to standard systemic therapy significantly reduced CTC levels after 3 mo of treatment and normalized levels remained steady throughout 18 months follow up. A significant correlation was observed between CTC and BTM after 18 months of treatment with ZA.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-06.