title: Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)].
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Banys
authors.forename: Erich-Franz
authors.initials: EF
authors.lastname: Solomayer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gebauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Natalia
authors.initials: N
authors.lastname: Krawczyk
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lueck
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kraemer
authors.forename: Birgit
authors.initials: B
authors.lastname: Wackwitz
authors.forename: Peter
authors.initials: P
authors.lastname: Hirnle
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.affiliation: Department of Gynecology and Obstetrics, Heinrich-Heine University of Düsseldorf, Moorenstr, 5, 40225, Düsseldorf, Germany. tanja.fehm@t-online.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D059186:Chemoradiotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D013997:Time Factors; D047368:Tumor Burden; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid