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Open Access 01-05-2019 | Breast Cancer | Clinical trial

Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)—PathIES

Authors: Zsolt Szijgyarto, Koen D. Flach, Mark Opdam, Carlo Palmieri, Sabine C. Linn, Jelle Wesseling, Simak Ali, Judith M. Bliss, Maggie Chon U. Cheang, Wilbert Zwart, R. Charles Coombes

Published in: Breast Cancer Research and Treatment | Issue 1/2019

Abstract

Purpose

The prognostic and predictive values of the MAPK/AKT/ERα phosphorylation axis (pT202/T204MAPK, pT308AKT, pS473AKT, pS118ERα and pS167ERα) in primary tumours were assessed to determine whether these markers can differentiate between patient responses for switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane and continued tamoxifen monotherapy in the Intergroup Exemestane Study (IES).

Methods

Of the 4724 patients in IES, 1506 were managed in a subset of centres (N = 89) participating in PathIES. These centres recruited 1282 (85%, 1282/1506) women into PathIES of whom 1036 had phospho-marker data. All phospho-markers were analysed by immunohistochemistry staining. Multivariable Cox proportional hazards models of the phospho-markers for disease-free survival (DFS) and overall survival (OS) were adjusted for clinicopathological factors. Treatment effects on the biomarker expression were determined by interaction tests. Benjamini–Hochberg adjustment for multiple testing with a false discovery rate of 10% was applied (p_BH).

Results

Phospho-T202/T204MAPK, pS118ERα and pS167ERα were all found to be correlated (p_BH = 0.0002). These markers were not associated with either DFS or OS when controlling for the established clinicopathological factors. Interaction terms between the phospho-markers and treatment strategies for either DFS or OS were not statistically significant (p_BH > 0.05 for all).

Conclusions

This PathIES study confirmed previously described associations between the phosphorylation site markers of AKT, MAPK and ERα activity in postmenopausal breast cancer patients. No prognostic correlations between the phosphorylation markers and clinical outcome were found, nor were they predictive for clinical outcomes among patients who switched therapy over those treated with tamoxifen alone.

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Title: Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)—PathIES
Authors: Zsolt Szijgyarto
Koen D. Flach
Mark Opdam
Carlo Palmieri
Sabine C. Linn
Jelle Wesseling
Simak Ali
Judith M. Bliss
Maggie Chon U. Cheang
Wilbert Zwart
R. Charles Coombes
Publication date: 01-05-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Tamoxifen
Exemestane
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 1/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-05110-x

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