Speirs, V, Viale, G, Mousa, K et al. (14 more authors) (2015) Prognostic and predictive value of ERβ1 and ERβ2 in the Intergroup Exemestane Study (IES) - first results from PathIES. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. ISSN 0923-7534
Abstract
BACKGROUND: IES was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane. PathIES aimed to assess the potential prognostic and predictive value of ERβ1 and ERβ2 expression in primary tumours in order to determine benefit in the two treatment arms. PATIENTS AND METHODS: Primary tumour samples were available for 1256 patients (27% IES population). ERβ1 and ERβ2 expression was dichotomised at the median IHC score (high if ERβ1≥191, ERβ2≥164). Hazard ratios (HR) were estimated by multivariable Cox proportional hazards models adjusting for clinicopathological factors. Treatment effects with biomarker expressions were determined by interaction tests. Analysis explored effects of markers both as a continuous variable and with dichotomised cut offs. RESULTS: Neither ERβ1 nor ERβ2 were associated with disease free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ERβ1 expression compared with low was associated with better DFS (HR=0.38:95%CI; 0.21-0.68, p=0.001). DFS benefit of exemestane over tamoxifen (HR=0.40:95%CI; 0.22-0.70) was found in the low ERβ1 subgroup (interaction p=0.01). No significant difference with treatment was observed for ERβ2 expression in either DFS or OS. CONCLUSION: In the PathIES population exemestane appeared to be superior to tamoxifen among patients with low ERβ1 expression but not in those with high ERβ1 expression. This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor as compared to tamoxifen and an independent validation is warranted.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015, Oxford University Press. This is an author produced version of a paper published in Annals of oncology. Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | PathIES Sub-Committee |
Dates: |
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Institution: | The University of Leeds |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Jun 2015 09:57 |
Last Modified: | 23 May 2016 06:04 |
Published Version: | http://dx.doi.org/%2010.1093/annonc/mdv242 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/annonc/mdv242 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86647 |