title: 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study.
abstract: OBJECTIVE
  To assess the long term effectiveness of adjuvant treatment with cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with operable breast cancer at risk of relapse, on the basis of three successive randomised trials and one observational study conducted from June 1973 to December 1980.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Istituto Nazionale Tumori in Milan, Italy.
  
  
  METHODS
  Relapse free and overall survival, measured by univariate and multivariate analyses.
  
  
  RESULTS
  After a median follow up of 28.5 years for the initial study, adjuvant CMF was found to reduce the relative risk of relapse significantly (hazard ratio 0.71, 95% confidence interval 0.56 to 0.91, P = 0.005) and death (0.79, 0.63 to 0.98, P = 0.04). Administration of CMF for 12 cycles does not seem superior to a shorter administration of six cycles. In the node negative and oestrogen receptor negative trial, intravenous CMF significantly reduced the relative risk of relapse of disease (0.65, 0.47 to 0.90, P = 0.009) and death (0.65, 0.47 to 0.92, P = 0.01) at a median follow up of 20 years.
  
  
  CONCLUSIONS
  When delivered optimally, CMF benefits patients at risk of relapse of distant disease without evidence of detrimental effects in any of the examined subgroups.
authors.affiliation: Istituto Nazionale Tumori, 20133 Milan, Italy. gianni.bonadonna@istitutotumori.mi.it
authors.forename: Gianni
authors.initials: G
authors.lastname: Bonadonna
authors.forename: Angela
authors.initials: A
authors.lastname: Moliterni
authors.forename: Milvia
authors.initials: M
authors.lastname: Zambetti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
mesh_terms: D000328:Adult; D000368:Aged; D000568:Amenorrhea / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate