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

H. M. Earl; L. Hiller; J. A. Dunn; A. L. Vallier; S. J. Bowden; S. D. Jordan; F. Blows; A. Munro; S. Bathers; R. Grieve; D. A. Spooner; R. Agrawal; I. Fernando; A. M. Brunt; S. M. O'Reilly; S. M. Crawford; Daniel Rea; 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

doi:10.1038/bjc.2012.370

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

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

^*Corresponding author for this work

Cancer Clinical Trials Unit

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1257-1267
Number of pages	11
Journal	British Journal of Cancer
Volume	107
Issue number	8
DOIs	https://doi.org/10.1038/bjc.2012.370
Publication status	Published - 9 Oct 2012

Keywords

Adjuvant chemotherapy
Anthracyclines
Breast cancer
Classical CMF
Epirubicin
NEAT

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/bjc.2012.370

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

Earl, H. M., Hiller, L., Dunn, J. A., Vallier, A. L., Bowden, S. J., Jordan, S. D., Blows, F., Munro, A., Bathers, S., Grieve, R., Spooner, D. A., Agrawal, R., Fernando, I., Brunt, A. M., O'Reilly, S. M., Crawford, S. M., Rea, D., Simmonds, P., Mansi, J. L., ... Poole, C. J. (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), 1257-1267. https://doi.org/10.1038/bjc.2012.370

@article{7b0f8769cfb740fb8cdc6f5fbd0c0fe9,

title = "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",

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.",

keywords = "Adjuvant chemotherapy, Anthracyclines, Breast cancer, Classical CMF, Epirubicin, NEAT",

author = "Earl, {H. M.} and L. Hiller and Dunn, {J. A.} and Vallier, {A. L.} and Bowden, {S. J.} and Jordan, {S. D.} and F. Blows and A. Munro and S. Bathers and R. Grieve and Spooner, {D. A.} and R. Agrawal and I. Fernando and Brunt, {A. M.} and O'Reilly, {S. M.} and Crawford, {S. M.} and Daniel Rea and P. Simmonds and Mansi, {J. L.} and A. Stanley and K. McAdam and L. Foster and Leonard, {R. Cf} and Twelves, {C. J.} and D. Cameron and Bartlett, {J. Ms} and P. Pharoah and E. Provenzano and C. Caldas and Poole, {C. J.}",

year = "2012",

month = oct,

day = "9",

doi = "10.1038/bjc.2012.370",

language = "English",

volume = "107",

pages = "1257--1267",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Cancer Research UK",

number = "8",

}

Earl, HM, Hiller, L, Dunn, JA, Vallier, AL, 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, D, Simmonds, P, Mansi, JL, Stanley, A, McAdam, K, Foster, L, Leonard, RC, Twelves, CJ, Cameron, D, Bartlett, JM, Pharoah, P, Provenzano, E, Caldas, C & 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, vol. 107, no. 8, pp. 1257-1267. https://doi.org/10.1038/bjc.2012.370

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. / Earl, H. M.; Hiller, L.; Dunn, J. A. et al.
In: British Journal of Cancer, Vol. 107, No. 8, 09.10.2012, p. 1257-1267.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer

T2 - Results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials

AU - Earl, H. M.

AU - Hiller, L.

AU - Dunn, J. A.

AU - Vallier, A. L.

AU - Bowden, S. J.

AU - Jordan, S. D.

AU - Blows, F.

AU - Munro, A.

AU - Bathers, S.

AU - Grieve, R.

AU - Spooner, D. A.

AU - Agrawal, R.

AU - Fernando, I.

AU - Brunt, A. M.

AU - O'Reilly, S. M.

AU - Crawford, S. M.

AU - Rea, Daniel

AU - Simmonds, P.

AU - Mansi, J. L.

AU - Stanley, A.

AU - McAdam, K.

AU - Foster, L.

AU - Leonard, R. Cf

AU - Twelves, C. J.

AU - Cameron, D.

AU - Bartlett, J. Ms

AU - Pharoah, P.

AU - Provenzano, E.

AU - Caldas, C.

AU - Poole, C. J.

PY - 2012/10/9

Y1 - 2012/10/9

N2 - 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.

AB - 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.

KW - Adjuvant chemotherapy

KW - Anthracyclines

KW - Breast cancer

KW - Classical CMF

KW - Epirubicin

KW - NEAT

UR - http://www.scopus.com/inward/record.url?scp=84867379438&partnerID=8YFLogxK

U2 - 10.1038/bjc.2012.370

DO - 10.1038/bjc.2012.370

M3 - Article

C2 - 23047592

AN - SCOPUS:84867379438

SN - 0007-0920

VL - 107

SP - 1257

EP - 1267

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -