Journal article

Constitutive phosphorylated STAT3-associated gene signature is predictive for trastuzumab resistance in primary HER2-positive breast cancer

A Sonnenblick, S Brohée, D Fumagalli, D Vincent, D Venet, M Ignatiadis, R Salgado, G Eynden, F Rothé, C Desmedt, P Neven, S Loibl, C Denkert, H Joensuu, S Loi, N Sirtaine, PL Kellokumpu-Lehtinen, M Piccart, C Sotiriou

BMC Medicine | BIOMED CENTRAL LTD | Published : 2015

Abstract

Background: The likelihood of recurrence in patients with breast cancer who have HER2-positive tumors is relatively high, although trastuzumab is a remarkably effective drug in this setting. Signal transducer and activator of transcription 3 protein (STAT3), a transcription factor that is persistently tyrosine-705 phosphorylated (pSTAT3) in response to numerous oncogenic signaling pathways, activates downstream proliferative and anti-apoptotic pathways. We hypothesized that pSTAT3 expression in HER2-positive breast cancer will confer trastuzumab resistance. Methods: We integrated reverse phase protein array (RPPA) and gene expression data from patients with HER2-positive breast cancer treate..

View full abstract

Grants

Awarded by Breast Cancer Research Foundation


Funding Acknowledgements

We would like to thank all the patients who participated in the trials and their families, and Carolyn Straehle for her editorial assistance. AS is an ESMO translational research fellow. This research project was supported by ESMO with the aid of a grant from Roche. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche. This work is part of the EU-FP7 project RESPONSIFY, grant no: 278659. CS is supported by the Breast Research Cancer Foundation (BCRF).