Research article
Lack of EGFR activating mutations in European patients with triple negative breast cancer could emphasize geographic and ethnic variations in breast cancer mutation profiles
Breast Cancer Research 2011, 13:R133 doi:10.1186/bcr3079
Published: 22 December 2011Abstract (provisional)
Introduction
Triple negative breast cancers (TNBC) are characterized by lack of expression of hormone receptors and HER-2. As they frequently express Epidermal Growth Factor Receptors (EGFR), 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 from an East Asian population. Since variations in the frequency of EGFR activating mutations in East Asians and other populations with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC.
Methods
We 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 exon 19 and 21 of EGFR. Results were then confirmed by bi-directional sequencing of all samples
Results
HRM analysis allowed the detection of three EGFR exon 21 mutations but no exon 19 mutation. There was a 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.
Conclusions
This 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.