title: High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial.
abstract: BACKGROUND
  The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes.
  
  
  METHODS
  Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat.
  
  
  RESULTS
  At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm.
  
  
  CONCLUSIONS
  At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.
authors.affiliation: Cancer Research UK Department of Cancer Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London. c.coombes@imperial.ac.uk
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: M
authors.initials: M
authors.lastname: Emson
authors.forename: C
authors.initials: C
authors.lastname: Peckitt
authors.forename: C
authors.initials: C
authors.lastname: Gallagher
authors.forename: C
authors.initials: C
authors.lastname: Bengala
authors.forename: A
authors.initials: A
authors.lastname: Tres
authors.forename: R
authors.initials: R
authors.lastname: Welch
authors.forename: P
authors.initials: P
authors.lastname: Lawton
authors.forename: R
authors.initials: R
authors.lastname: Rubens
authors.forename: E
authors.initials: E
authors.lastname: Woods
authors.forename: J
authors.initials: J
authors.lastname: Haviland
authors.forename: D
authors.initials: D
authors.lastname: Vigushin
authors.forename: E
authors.initials: E
authors.lastname: Kanfer
authors.forename: J M
authors.initials: JM
authors.lastname: Bliss
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007391:International Cooperation; D008198:Lymph Nodes / Q000473:pathology*; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000473:pathology; D009367:Neoplasm Staging; D018579:Patient Selection; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012016:Reference Values; D018570:Risk Assessment; D033581:Stem Cell Transplantation / Q000379:methods*; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome