Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profilesReport as inadecuate




Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles - Download this document for free, or read online. Document in PDF available to download.

Breast Cancer Research

, 13:R133

First Online: 22 December 2011Received: 18 August 2011Revised: 13 December 2011Accepted: 22 December 2011

Abstract

IntroductionTriple-negative breast cancers TNBCs are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 HER-2. As they frequently express epidermal growth factor receptors EGFRs, anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC.

MethodsWe selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting HRM analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples.

ResultsHRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified.

ConclusionsThis study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population.

Abbreviationsbpbase pair

BRCA1breast cancer type 1 susceptibility protein

Ctcycle threshold

EDTAethylenediaminetetraacetic acid

EGFRepidermal growth factor receptor

ERoestrogen receptor

HER-2epidermal growth factor receptor 2

HRMhigh-resolution melting

IHCimmunohistochemistry

MXno clinical data regarding metastatic spreading

NEnot evaluated

NSCLCnon-small-cell lung cancer

PCRpolymerase chain reaction

PRprogesterone receptor

RTreverse transcriptase

SNPsingle-nucleotide polymorphism

TNBCtriple-negative breast cancer

TXno clinical data regarding tumour size.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr3079 contains supplementary material, which is available to authorized users.

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Author: William Jacot - Evelyne Lopez-Crapez - Simon Thezenas - Romain Senal - Frédéric Fina - Frédéric Bibeau - Gilles Romieu

Source: https://link.springer.com/



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