Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

BMC Cancer

Malgorzata Banys⁵  Erich-Franz Solomayer⁴  Gerhard Gebauer⁵  Wolfgang Janni²  Natalia Krawczyk³  Hans-Joachim Lueck⁹  Sven Becker⁸  Jens Huober³  Bernhard Kraemer⁷  Birgit Wackwitz¹  Peter Hirnle⁶  Diethelm Wallwiener⁷  Tanja Fehm³ 

[1] Novartis Oncology, Nuremberg, Germany

[2] Department of Gynecology and Obstetrics, University of Ulm, Ulm, Germany

[3] Department of Gynecology and Obstetrics, Heinrich-Heine University of Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

[4] Department of Gynecology and Obstetrics, University Hospital of Saarland, Homburg, Germany

[5] Department of Gynecology and Obstetrics, Marienkrankenhaus Hamburg, Hamburg, Germany

[6] Central Academic Hospital, Department of Radiation Oncology, Bielefeld, Germany

[7] Department of Gynecology and Obstetrics, University of Tuebingen, Tuebingen, Germany

[8] Department of Gynecology and Obstetrics, University of Frankfurt, Frankfurt, Germany

[9] Department of Gynecologic Oncology, Hannover Medical School, Hannover, Germany

关键词: Survival;    Disseminated tumor cells;    Zoledronate;    Bisphosphonates;    Breast cancer;   

Others  :  1079512
DOI  :  10.1186/1471-2407-13-480

 received in 2013-04-24, accepted in 2013-09-26,  发布年份 2013

【 摘 要 】

Background

The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068).

Methods

Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated.

Results

86 patients could be included into survival analysis (median follow-up: 88 months, range: 8–108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011).

Conclusions

Bisphosphonate therapy contributes to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC.

Trial registration

ClinicalTrials.gov Identifier:NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)].

【 授权许可】

   
2013 Banys et al.; licensee BioMed Central Ltd.

【 图 表 】

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