Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer

Anticancer Res. 2010 May;30(5):1807-13.

Abstract

Background: There is strong evidence for the isolated tumour cells (ITCs) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up. The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC.

Patients and methods: A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up. Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy. In a matched-pair analysis, these patients were compared to 141 patients who did not receive additional zoledronate treatment. The bone marrow was re-examined after a median of 7.9 months (SD 0.89) and 11.5 months (SD 12.41; p=0.11), respectively. Patients were followed-up prospectively for a median of 39 months after the first aspiration.

Results: While ITCs were detected in all 172 patients at the time of first bone marrow aspiration, ITCs were detected in four patients (13%) following 6 months of zoledronate therapy in contrast to 38 patients (27%) of the control group (p=0.099). The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group (p=0.02 vs. p=0.14). Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival (p=0.05).

Conclusion: These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Density Conservation Agents / therapeutic use
  • Bone Marrow / pathology
  • Bone Marrow Cells / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cell Cycle
  • Chemotherapy, Adjuvant
  • Diphosphonates / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Middle Aged
  • Models, Statistical
  • Recurrence
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid