title: Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles.
abstract: BACKGROUND
  Triple-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.
  
  
  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 exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples.
  
  
  RESULTS
  HRM 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.
  
  
  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.
authors.affiliation: Département d'Oncologie Médicale, CRLC Val d'Aurelle-Paul Lamarque, 208, rue des Apothicaires, F-34298, France. william.jacot@valdorel.fnclcc.fr
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lopez-Crapez
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.forename: Romain
authors.initials: R
authors.lastname: Senal
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fina
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics
chemical_list: D066246:ErbB Receptors