title: Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up.
abstract: BACKGROUND
  Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil was administered after radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes to assess whether it would improve treatment outcome as compared with surgery alone. Here we report a 20-year follow-up of this investigation.
  
  
  METHODS
  In 1973 we began a trial involving 386 women who were randomly assigned to receive either no further treatment after radical mastectomy (179 women) or 12 monthly cycles of adjuvant combination chemotherapy (207 women). All patients were admitted to the Istituto Nazionale Tumori in Milan, Italy. Adjuvant chemotherapy was delivered in the outpatient clinic of the Division of Medical Oncology.
  
  
  RESULTS
  After a median follow-up of 19.4 years, the patients given adjuvant combination chemotherapy had significantly better rates of relapse-free survival (unadjusted relative risk of relapse, 0.71; 95 percent confidence interval, 0.56 to 0.90; P = 0.004; adjusted relative risk, 0.65, 95 percent confidence interval, 0.51 to 0.83; P < 0.001) and total survival (unadjusted relative risk of death, 0.78; 95 percent confidence interval, 0.62 to 0.99; P = 0.04; adjusted relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P = 0.03). With the exception of postmenopausal women, a benefit from adjuvant chemotherapy was evident in all subgroups of patients.
  
  
  CONCLUSIONS
  The long-term results of this trial of adjuvant combination chemotherapy confirm our preliminary observations of the effectiveness of the treatment in women with node-positive breast cancer.
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bonadonna
authors.forename: P
authors.initials: P
authors.lastname: Valagussa
authors.forename: A
authors.initials: A
authors.lastname: Moliterni
authors.forename: M
authors.initials: M
authors.lastname: Zambetti
authors.forename: C
authors.initials: C
authors.lastname: Brambilla
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D015409:Mastectomy, Radical; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate