edoc

Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

Rasmussen, Birgitte B. and Regan, Meredith M. and Lykkesfeldt, Anne E. and Dell'Orto, Patrizia and Del Curto, Barbara and Henriksen, Katrine L. and Mastropasqua, Mauro G. and Price, Karen N. and Méry, Eliane and Lacroix-Triki, Magali and Braye, Stephen and Altermatt, Hans J. and Gelber, Richard D. and Castiglione-Gertsch, Monica and Goldhirsch, Aron and Gusterson, Barry A. and Thürlimann, Beat and Coates, Alan S. and Viale, Giuseppe. (2008) Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. The Lancet oncology, Vol. 9. pp. 23-28.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6004070

Downloads: Statistics Overview

Abstract

BACKGROUND: The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. METHODS: The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range >1 to 90 months]). A central assessment of oestrogen receptor (ER), progesterone receptor (PgR) and ERBB2 status using paraffin-embedded primary tumour material was possible for 3650 (74%) patients. ER, PgR, and ERBB2 expression were measured by immunohistochemistry (IHC) and ERBB2-positivity was confirmed by fluorescence in-situ hybridisation (FISH). Positive staining in at least 1% of cells was considered to show presence of ER or PgR expression. Tumours were deemed ERBB2-positive if amplified by FISH, or, for the few tumours with unassessable or unavailable FISH results, if they were IHC 3+. Hazard ratios (HR) estimated by Cox modelling were used to compare letrozole with tamoxifen for DFS, which was the primary endpoint, and to assess treatment-by-covariate interactions. The BIG 1-98 trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00004205. FINDINGS: By central assessment 7% (257 of 3650) of tumours were classified as ERBB2-positive. In 3533 patients with tumours confirmed to express ER, DFS was poorer in patients with ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumo (n=3294; HR 2.09 [95% CI 1.59-2.76]; p>0.0001). There was no statistical evidence of heterogeneity in the treatment effect according to ERBB2 status of the tumour (p=0.60 for interaction), thus, letrozole improves DFS compared with tamoxifen regardless of ERBB2 status. The observed HRs were 0.62 (95% CI 0.37-1.03) for ERBB2-positive tumours and 0.72 (0.59-0.87) for ERBB2-negative tumours. INTERPRETATION: A benefit of letrozole over tamoxifen was noted, irrespective of ERBB2 status of the tumour, and, therefore, ERBB2 status does not seem to be a selection criterion for treatment with letrozole versus tamoxifen in postmenopausal women with endocrine-responsive early breast cancer.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Onkologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Onkologie
UniBasel Contributors:Thürlimann, Beat
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:1470-2045
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:11 Oct 2012 15:32
Deposited On:11 Oct 2012 15:29

Repository Staff Only: item control page