Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: Results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials

Research output: Contribution to journalArticlepeer-review


  • H. M. Earl
  • L. Hiller
  • J. A. Dunn
  • A. L. Vallier
  • S. D. Jordan
  • F. Blows
  • A. Munro
  • R. Grieve
  • D. A. Spooner
  • R. Agrawal
  • I. Fernando
  • A. M. Brunt
  • S. M. O'Reilly
  • S. M. Crawford
  • P. Simmonds
  • J. L. Mansi
  • A. Stanley
  • K. McAdam
  • L. Foster
  • R. Cf Leonard
  • C. J. Twelves
  • D. Cameron
  • J. Ms Bartlett
  • P. Pharoah
  • E. Provenzano
  • C. Caldas
  • C. J. Poole

Colleges, School and Institutes

External organisations

  • University of Cambridge
  • NIHR Cambridge Biomedical Research Centre
  • University of Warwick
  • Cambridge University Hospitals NHS Foundation Trust
  • University of Edinburgh
  • University Hospitals Coventry and Warwickshire NHS Trust
  • Queen Elizabeth Hospital Birmingham
  • Shrewsbury and Telford NHS Trust
  • University Hospitals of North Midlands NHS Trust
  • Clatterbridge Hospital
  • Airedale General Hospital
  • Royal South Hampshire Hospital
  • Guy's and St Thomas' NHS Foundation Trust
  • King’s College London
  • Peterborough City Hospital
  • Scottish Cancer Therapy Network
  • Imperial College Healthcare NHS Trust
  • University of Leeds
  • Western General Hospitals NHS Trust
  • Strangeways Research Laboratory
  • Clinical Sciences Research Institute


Background: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. Methods: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. Results: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65-0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65-0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. Conclusion: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.


Original languageEnglish
Pages (from-to)1257-1267
Number of pages11
JournalBritish Journal of Cancer
Issue number8
Publication statusPublished - 9 Oct 2012


  • Adjuvant chemotherapy, Anthracyclines, Breast cancer, Classical CMF, Epirubicin, NEAT

ASJC Scopus subject areas

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