title: One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer.
abstract: OBJECTIVE
  We report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes.
  
  
  METHODS
  Postmenopausal patients with breast cancer and positive nodes, deep invasion or size exceeding 5 cm were randomly assigned to 1 year of tamoxifen, or cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 intravenously on day 1 every 4 weeks for nine cycles plus tamoxifen (CMFT). Tissue microarrays were constructed retrospectively and oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and proliferation-related Ki-67 antigen (Ki67) status were assessed.
  
  
  RESULTS
  From October 1982 through March 1990 we randomised 1445 patients and 969 (67%) were eligible for the biomarker analysis. At 10-years 936 women had suffered a disease-free survival (DFS) event (tamoxifen, 495 events in 686 patients; CMFT, 441 events in 642 patients). The addition of CMF to tamoxifen significantly improved DFS (adjusted hazard ratio 0.82; 95% confidence interval (CI) 0.71-0.93; P = 0.003) but not overall survival (adjusted hazard ratio 0.95; 95% CI 0.85-1.08; P = 0.44). DFS was superior in Luminal A tumours (ER or PgR positive, HER2 negative and Ki67 ≤ 14%) when compared to Luminal B or non-luminal (ER and PgR negative) tumours. There was no statistical evidence of heterogeneity by subtype in the benefit from CMF (P(interaction) = 0.45).
  
  
  CONCLUSIONS
  CMF added to 1 year of tamoxifen reduces the risk of a DFS event. The benefit from CMF was not significantly different in Luminal A and B subtypes.
authors.affiliation: Danish Breast Cancer Cooperative Group (DBCG), Rigshospitalet, Copenhagen, Denmark. ejlertsen@rh.dk
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Jensen
authors.forename: Johanna
authors.initials: J
authors.lastname: Elversang
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Rasmussen
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: Jørn
authors.initials: J
authors.lastname: Andersen
authors.forename: Dorte L
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Søren
authors.initials: S
authors.lastname: Cold
authors.forename: Henning T
authors.initials: HT
authors.lastname: Mouridsen
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D017698:Postmenopause; D012042:Registries / Q000706:statistics & numerical data; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate
keywords: Adjuvant therapy; Breast cancer; Cyclophosphamide; Fluorouracil; Methotrexate; Tamoxifen