Imperial College London

ProfessorSimakAli

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Molecular Endocrine Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2811simak.ali

 
 
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Location

 

133ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Szijgyarto:2019:10.1007/s10549-018-05110-x,
author = {Szijgyarto, Z and Flach, KD and Opdam, M and Palmieri, C and Linn, SC and Wesseling, J and Ali, S and Bliss, JM and Cheang, MCU and Zwart, W and Coombes, RC},
doi = {10.1007/s10549-018-05110-x},
journal = {Breast Cancer Research and Treatment},
pages = {149--163},
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},
url = {http://dx.doi.org/10.1007/s10549-018-05110-x},
volume = {175},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - PurposeThe 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).MethodsOf 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 (pBH).ResultsPhospho-T202/T204MAPK, pS118ERα and pS167ERα were all found to be correlated (pBH = 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 (pBH > 0.05 for all).ConclusionsThis 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.
AU - Szijgyarto,Z
AU - Flach,KD
AU - Opdam,M
AU - Palmieri,C
AU - Linn,SC
AU - Wesseling,J
AU - Ali,S
AU - Bliss,JM
AU - Cheang,MCU
AU - Zwart,W
AU - Coombes,RC
DO - 10.1007/s10549-018-05110-x
EP - 163
PY - 2019///
SN - 0167-6806
SP - 149
TI - 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
T2 - Breast Cancer Research and Treatment
UR - http://dx.doi.org/10.1007/s10549-018-05110-x
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000466424600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://link.springer.com/article/10.1007%2Fs10549-018-05110-x
UR - http://hdl.handle.net/10044/1/72981
VL - 175
ER -