title: Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial.
abstract: BACKGROUND
  We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety.
  
  
  METHODS
  BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740.
  
  
  RESULTS
  Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC.
  
  
  CONCLUSIONS
  Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation.
  
  
  BACKGROUND
  Sanofi.
authors.affiliation: Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Janusz
authors.initials: J
authors.lastname: Rolski
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guastalla
authors.forename: Amer
authors.initials: A
authors.lastname: Sami
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.forename: Eva
authors.initials: E
authors.lastname: Juhos
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardley
authors.forename: Tommy
authors.initials: T
authors.lastname: Fornander
authors.forename: John
authors.initials: J
authors.lastname: Hainsworth
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Modiano
authors.forename: Jeferson
authors.initials: J
authors.lastname: Vinholes
authors.forename: Tamas
authors.initials: T
authors.lastname: Pinter
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rodríguez-Lescure
authors.forename: Bruce
authors.initials: B
authors.lastname: Colwell
authors.forename: Pierre
authors.initials: P
authors.lastname: Whitlock
authors.forename: Louise
authors.initials: L
authors.lastname: Provencher
authors.forename: Kara
authors.initials: K
authors.lastname: Laing
authors.forename: David
authors.initials: D
authors.lastname: Walde
authors.forename: Chris
authors.initials: C
authors.lastname: Price
authors.forename: Judith C
authors.initials: JC
authors.lastname: Hugh
authors.forename: Barrett H
authors.initials: BH
authors.lastname: Childs
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bassi
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Lindsay
authors.forename: Véronique
authors.initials: V
authors.lastname: Wilson
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rupin
authors.forename: Vincent
authors.initials: V
authors.lastname: Houé
authors.forename: Charles
authors.initials: C
authors.lastname: Vogel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human