title: How should we introduce high-dose chemotherapeutic strategies into the adjuvant management of high-risk breast cancer in Australasia?
abstract: BACKGROUND
  Development of bone marrow support techniques has altered the standard chemotherapeutic management of haematological malignancies, and these techniques are now being increasingly utilized in solid tumours. In breast cancer, survival benefits have resulted from conventional dose adjuvant chemotherapy, but outcomes remain poor in many women with high-risk disease. Improved response rates with high-dose chemotherapy (HDC) in metastatic disease have led to the investigation of these techniques in adjuvant therapy of high-risk localized disease. In some high-risk patient subgroups survival is extremely poor, with 5-year rates below 30%. Improved adjuvant strategies for patients in these subgroups are therefore urgently required. In Australasia, oncology departments are currently considering accrual of women with high-risk disease into the International Breast Cancer Study Group (IBCSG) 15-95 Trial investigating HDC/stem cell transplantation.
  
  
  METHODS
  The present paper reviews the available data on the efficacies and toxicities of currently available high-dose chemotherapeutic strategies; discussing methodological considerations relevant to their introduction and safe use in the adjuvant setting in Australia and New Zealand.
  
  
  RESULTS
  Although response rates with HDC in metastatic disease are encouraging, the clinical effectiveness of current HDC regimens in adjuvant management has not been established and is limited by significant toxicity.
  
  
  CONCLUSIONS
  The introduction of HDC strategies for high-risk breast cancer in Australia encounters difficulties both in trial design and potential clinical practice.
authors.affiliation: Department of Radiation Oncology, Newcastle Mater Hospital, Waratah, New South Wales, Australia. mdmfba@cc.newcastle.edu.au
authors.forename: M
authors.initials: M
authors.lastname: Back
authors.forename: G
authors.initials: G
authors.lastname: Delaney
authors.forename: J
authors.initials: J
authors.lastname: Denham
authors.forename: P
authors.initials: P
authors.lastname: Graham
authors.forename: C
authors.initials: C
authors.lastname: Hamilton
authors.forename: G
authors.initials: G
authors.lastname: Morgan
authors.forename: P
authors.initials: P
authors.lastname: O'Brien
authors.forename: P
authors.initials: P
authors.lastname: Yuile
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000628:therapy; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D012308:Risk Management
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate