title: [Efficacy of zoledronate in treating persisting isolated tumor cells in bone marrow in patients with breast cancer. A phase II pilot study].
abstract: OBJECTIVE
  Recently the highest level of evidence indicated the prognostic value of isolated tumor cells (ITC) in bone marrow of patients with breast cancer, both at primary diagnosis and during recurrence-free follow-up. The aim of the present study was to investigate the therapeutic efficacy of zoledronate in reducing persistence of ITC in the bone marrow of patients with breast cancer after they had completed primary therapy.
  
  
  METHODS
  In a non-randomized phase II pilot study, 4 mg of zoledronate were administered once every four weeks for six months, after a initial loading dose of 8 mg, to 31 patients with persisting ITC in bone marrow. All patients had completed surgery and adjuvant chemotherapy, if indicated, at least 6 months previously. The bone marrow was re-examined after 7.9 months (std 0,89). ITC were detected by immunocytochemical staining, using the monoclonal pan-cytokeratin antibody A45-B/B3 and the APAAP technique. Patients were followed-up prospectively for a median of 39 months after the first aspiration.
  
  
  RESULTS
  ITC were detected in all 31 patients at the time of first bone marrow aspiration, but 27 of them (87 %) were free of ITC 6 months after the end of zoledronate therapy. The reduction in cell numbers between first and second aspiration were statistically significance (P < 0,0001). Ten of 12 patients without detection of ITC in bone marrow after treatment and who had undergone additional aspirations, still had no ITC a median time of 19 months (range 4.7 - 38.7 months) after the end of treatment. Zoledronate treatment was well tolerated, bone pain having been the most common side effect in 45 % of patients (n = 14).
  
  
  CONCLUSIONS
  These results indicate a potential antineoplastic effect of zoledronate, a cell-cycle independent drug, on persisting ITC in a dormant state. Our data provide the basis for investigating the efficacy of zoledronate on ITC in treating primary breast cancer in prospectively randomized trials. ITC in bone marrow represents a useful marker in selecting patients at risk for recurrence and for monitoring therapeutic efficacy.
authors.affiliation: Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Innenstadt der Ludwig-Maximilians-Universität München. brigitte.rack@med.uni-muenchen.de
authors.forename: B
authors.initials: B
authors.lastname: Rack
authors.forename: C
authors.initials: C
authors.lastname: Schindlbeck
authors.forename: B
authors.initials: B
authors.lastname: Strobl
authors.forename: H
authors.initials: H
authors.lastname: Sommer
authors.forename: K
authors.initials: K
authors.lastname: Friese
authors.forename: W
authors.initials: W
authors.lastname: Janni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000517:prevention & control*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D010146:Pain / Q000139:chemically induced; D010865:Pilot Projects; D011379:Prognosis; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid