title: Effect of ibandronate on disseminated tumor cells in the bone marrow of patients with primary breast cancer: a pilot study.
abstract: BACKGROUND
  Breast cancer patients may experience disease relapse even 10-20 years after primary diagnosis. Recurrence is caused by dormant disseminated tumor cells (DTCs) in the bone marrow (BM). Whereas chemotherapy is unable to eradicate these non-proliferating cells, bisphosponates are currently being discussed as eliminating DTCs. The purpose of our study was to: i) analyze the presence of DTCs in the BM of breast cancer patients 2-10 years after first diagnosis of cancer, and ii) to study the effect of ibandronate on DTCs in those patients with DTC persistence.
  
  
  METHODS
  Bilateral BM aspirates of 54 individuals diagnosed 2-10 years ago with breast cancer, but currently disease free, were analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3. Patients with DTC persistence received oral ibandronate treatment (50 mg per day) for six months and bilateral BM aspirates were analyzed for DTCs again after therapy.
  
  
  RESULTS
  DTCs were found in 18/54 (33%) of the patients, with a median number of 3 disseminated tumor cells (range 1-6 cells). These 18 patients received ibandronate orally for 6 months and 17/18 patients were analyzed for DTCs again after therapy. Only 3/17 (18%) patients remained DTC-positive, with the detection of 1 (n=2 patients) and 3 DTCs, respectively. These three DTC-positive patients continued their ibandronate intake for a further six months and re-examination of the BM resulted in no detection of DTCs in any of the three patients.
  
  
  CONCLUSIONS
  Our pilot study indicates the potential effect of ibandronate on DTCs and further studies are needed to demonstrate these findings in a larger patient cohort.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany. oliver.hoffmann@uk-essen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Hoffmann
authors.forename: Bahriye
authors.initials: B
authors.lastname: Aktas
authors.forename: Cornelia
authors.initials: C
authors.lastname: Goldnau
authors.forename: Martin
authors.initials: M
authors.lastname: Heubner
authors.forename: Carsten
authors.initials: C
authors.lastname: Oberhoff
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007150:Immunohistochemistry; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D010865:Pilot Projects
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid