title: Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer.
abstract: BACKGROUND
  Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies.
  
  
  METHODS
  A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone.
  
  
  RESULTS
  The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days).
  
  
  CONCLUSIONS
  This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates.
authors.affiliation: Department of Medical Oncology, St Vincent's Hospital, Sydney, Australia. wsliauw@student.unsw.edu.au
authors.forename: Winston
authors.initials: W
authors.lastname: Liauw
authors.forename: Eva
authors.initials: E
authors.lastname: Segelov
authors.forename: Anna
authors.initials: A
authors.lastname: Lih
authors.forename: Ruth
authors.initials: R
authors.lastname: Dunleavy
authors.forename: Matthew
authors.initials: M
authors.lastname: Links
authors.forename: Robyn
authors.initials: R
authors.lastname: Ward
mesh_terms: D000368:Aged; D001847:Bone Diseases / Q000139:chemically induced*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002986:Clinical Trials as Topic; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077268:Pamidronate; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate