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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers

Authors: William Jacot, Caroline Mollevi, Frédéric Fina, Evelyne Lopez-Crapez, Pierre-Marie Martin, Pierre-Emmanuel Colombo, Frédéric Bibeau, Gilles Romieu, Pierre-Jean Lamy

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Triple negative breast cancers (TNBC) are a more aggressive subset of breast cancer. A better understanding of its biology could allow the rational development of targeted therapies.

Methods

We extensively analyzed the EGFR/PI3K/PTEN axis in a large, homogeneous population of TNBC to help defining the putative role of anti-EGFR and -PI3K targeted therapies in this setting. EGFR gene amplification, EGFR protein expression, PIK3CA and PTEN gene alterations (two members of EGFR downstream pathways) and their clinicopathological and prognostic implications were analyzed in 204 TNBC samples from European patients.

Results

EGFR amplification was detected in 18 of the 204 TNBC specimens (8.9 %) and was significantly associated with higher EGFR protein levels. Fourteen PIK3CA mutations were identified in exon 9 (6.7 %), and 17 in exon 20 (8.3 %). PIK3CA mutations, especially in exon 9, were significantly associated with grade I-II tumors. PTEN deletions were detected in 43 samples (21.50 %) and were significantly associated with grade III tumors (p < 0.001). Univariate analysis showed a significant association between relapse-free survival (RFS), T and N stage and exon 9 PIK3CA mutations. Overall survival was significantly associated with T stage, N stage and adjuvant chemotherapy, which was administered to 70.3 % of patients. In multivariate analyses, T stage, N stage, presence of exon 9 PIK3CA mutations and high EGFR protein level were independent poor prognostic factors for RFS, while adjuvant chemotherapy was associated with a better outcome.

Conclusions

High EGFR protein expression and exon 9 PIK3CA activating mutations are independent prognostic factors in TNBC. The efficacy of anti-PI3K targeted therapies needs to be evaluated in this setting.
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Metadata
Title
High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers
Authors
William Jacot
Caroline Mollevi
Frédéric Fina
Evelyne Lopez-Crapez
Pierre-Marie Martin
Pierre-Emmanuel Colombo
Frédéric Bibeau
Gilles Romieu
Pierre-Jean Lamy
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1977-3

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