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Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potential clinical significance

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Abstract

Zoledronic acid has direct and indirect antitumor effects. However, the optimal regimen for breast cancer patients remains to be determined. This study aimed to compare biomarker changes between a weekly low dose (metronomic arm) and a conventional dosage of zoledronic acid (conventional arm), and to explore correlations between biomarkers and progression-free survival (PFS). Sixty breast cancer patients with bone metastases were randomized to receive either zoledronic acid 1 mg IV weekly for 4 doses or a single dose of zoledronic acid 4 mg IV. Administration of other treatments was delayed for 1 month. Serial blood samples were collected on days 1, 15, 29, and at 3 months. Serum VEGF alteration was the primary endpoint. Compared to the conventional arm, the metronomic arm resulted in a significantly greater reduction in serum levels of VEGF and N-telopeptide of type I collagen (NTx) over time during the first month of treatment. Serum CA 15-3 level stabilized over time in the metronomic arm, but increased in the conventional arm. Independent prognostic factors for PFS included chemotherapy received (HR, 8.042; P = 0.000), estrogen receptor status (HR, 2.837; P = 0.020), VEGF levels at 3 months after intervention (HR, 2.026; P = 0.045), and baseline NTx (HR, 1.051; P = 0.001). Metronomic low-dose zoledronic acid is more effective than the conventional regimen and generates sustained reductions in circulating VEGF and NTx levels, as well as stabilization of serum CA 15-3 levels (ClinicalTrials.gov number, NCT00524849).

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Authors and Affiliations

  1. Department of Medical Oncology, Fudan University Cancer Hospital, No. 270, Dong An Road, Shanghai, 200032, China

    Xinmin Zhao, Haiyi Guo, Zhonghua Wang & Xichun Hu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Xinmin Zhao, Xiaofeng Xu, Lin Guo, Haiyi Guo, Jiong Wu, Zhimin Shao, Ji Zhu, Xiaomao Guo, Jiayi Chen, Beiling Zhu, Zhonghua Wang & Xichun Hu

  3. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China

    Xiaofeng Xu & Lin Guo

  4. Oncology & Faculty of Medicine, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Joseph Ragaz

  5. McGill University, Montreal, QC, Canada

    Joseph Ragaz

  6. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Jiong Wu & Zhimin Shao

  7. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

    Ji Zhu, Xiaomao Guo & Jiayi Chen

  8. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China

    Beiling Zhu

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  1. Xinmin Zhao
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Correspondence to Xichun Hu.

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Zhao, X., Xu, X., Guo, L. et al. Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potential clinical significance. Breast Cancer Res Treat 124, 733–743 (2010). https://doi.org/10.1007/s10549-010-1183-6

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  • DOI: https://doi.org/10.1007/s10549-010-1183-6

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