title: Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group.
abstract: BACKGROUND
  The contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer.
  
  
  METHODS
  Between March 1991 and June 1999, 1863 women with stages I-IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment. Irrespective of menstrual status and hormone receptor content of the primary tumour, patients were stratified by institute, chemotherapy scheme and age (above 50 years or younger). The main end-point was to detect a 5% increase in the 5 year survival (from 80% to 85%) in favour of antioestrogen therapy. Secondary end-points were relapse free survival (RFS), local control, incidence of second primary breast cancer and correlation of results with hormone receptor content.
  
  
  RESULTS
  After exclusion of all patients from three sites because of inadequate documentation, a total of 1724 patients (93%) were analysed (Tam 861 and Control 863). At a median follow-up of 6.5 years, 5-year RFS on tamoxifen was 73% versus 67% in controls (p=0.035). No difference was seen in overall survival. The benefit of tamoxifen therapy was mainly seen in the subgroup of patients with histologically documented positive axillary nodes (5-year RFS on tamoxifen 71% versus 64% in the control group, p=0.044) and in patients with tumours expressing the ER and PR positive phenotype (5-year RFS on tamoxifen 77% versus 70% in the control group, p=0.014).
  
  
  CONCLUSIONS
  Tamoxifen administered for 3 years after completion of adjuvant chemotherapy in this otherwise unselected group of patients for endocrine sensitivity had a limited impact on relapse and had no detectable effect on overall survival. The beneficial effect of tamoxifen is mainly confined to the subgroup of patients with node-positive disease and to patients with tumours expressing the ER and PR positive phenotype.
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Leilani
authors.initials: L
authors.lastname: Morales
authors.forename: Peter
authors.initials: P
authors.lastname: Canney
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dyczka
authors.forename: Emiel
authors.initials: E
authors.lastname: Rutgers
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
authors.forename: Marzena
authors.initials: M
authors.lastname: Welnicka-Jaskiewicz
authors.forename: Johan
authors.initials: J
authors.lastname: Nortier
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaerts
authors.forename: Patrick
authors.initials: P
authors.lastname: Therasse
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen