Earl, HM, Hiller, H, Vallier, A-L, Bowden, SJ, Jordan, SD, Blows, F, Munro, A, Bathers, S, Grieve, R, Spooner, DA, Agrawal, R, Fernando, I, Brunt, AM, O'Reilly, SM, Crawford, SM, Rea, DW, Simmonds, P, Mansi, JL, Stanley, A, McAdam, K, Foster, L, Leonard, RCF, Twelves, CJ, Cameron, D, Bartlett, JMS, Pharoah, P, Provenzano, E, Caldas, C and Poole, CJ (2012) 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. British Journal of Cancer, 107 (8). pp. 1257-1267.

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Abstract

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.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Nature Publishing Group at http://dx.doi.org/10.1038/bjc.2012.370 - please refer to any applicable terms of use of the publisher.
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 06 Apr 2017 15:18
Last Modified: 30 May 2019 13:40
URI: https://eprints.keele.ac.uk/id/eprint/3177

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