CEF is superior to CMF for tumours with aberrations: a Subpopulation Treatment Effect Pattern Plot (STEPP) analysis on Danish Breast Cancer Cooperative Group Study 89D

Katrín Á. Gunnarsdóttir (1) , Maj-Britt Jensen (1) , David Zahrieh (2) , Richard D. Gelber (2) , Ann Knoop (1) , Marco Bonetti (3) , Henning Mouridsen (1) , Bent Ejlertsen (1)

1 Danish Breast Cancer Cooperative Group (DBCG), DBCG Secretariat
2 Dana-Farber Cancer Institute [Boston]
3 Bocconi University

The aim of this study was to examine gene copy number changes as a means to identify groups of breast cancer patients with superior benefit from treatment with anthracyclines. Tumour tissue was retrospectively collected and successfully analysed for in 773 of 980 Danish patients randomly assigned to receive intravenous CMF (cyclophosphamide, methotrexate and fluorouracil) or CEF (cyclophosphamide, epirubicin and fluorouracil) in DBCG trial 89D. Subgroup analyses on this material published by Knoop et al. (J Clin Oncol 23:7483–7490, 2005) and updated by Nielsen et al. (Acta Oncol 47:725–734, 2008) demonstrated that superiority of CEF over CMF is limited to patients with aberrations, defined as patients whose tumours have ratio below 0.8 or above 2.0. The Subpopulation Treatment Effect Pattern Plot (STEPP) technique was applied to these data to explore the pattern of treatment effect relative to and to compare that pattern to the ranges previously used to define ‘aberrations'. The pattern of treatment effect illustrated by the STEPP analysis confirmed that the superiority of CEF over CMF is indeed limited to patients whose tumours have high or low ratios. The hypothesis of no treatment effect–covariate interaction was rejected ( = 0.02). Furthermore, results indicated that the interval of ratios hitherto denoted as ‘normal' could be narrower than previously assumed. A more optimal separation of subgroups could be obtained by altering cut-points currently used to define amplified and deleted tumours by narrowing the normal interval, and consequently enlarging the population with aberrated tumours.

Mots clés: Breast cancer; Treatment; Anthracycline; STEPP

Katrín Á. Gunnarsdóttir, Maj-Britt Jensen, David Zahrieh, Richard D. Gelber, Ann Knoop, et al.. CEF is superior to CMF for tumours with aberrations: a Subpopulation Treatment Effect Pattern Plot (STEPP) analysis on Danish Breast Cancer Cooperative Group Study 89D. Breast Cancer Research and Treatment, 2010, 123 (1), pp.163-169. ⟨10.1007/s10549-010-0931-y⟩. ⟨hal-00535817⟩