title: Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer.
abstract: BACKGROUND
  Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.
  
  
  METHODS
  Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.
  
  
  RESULTS
  We found no evidence of KRAS oncogenic mutations in all analyzed tumors.
  
  
  CONCLUSIONS
  This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Virgen de Victoria, Campus de Teatinos s/n, 29010 Málaga, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sánchez-Muñoz
authors.forename: Elena
authors.initials: E
authors.lastname: Gallego
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Luque
authors.forename: Luís G
authors.initials: LG
authors.lastname: Pérez-Rivas
authors.forename: Luís
authors.initials: L
authors.lastname: Vicioso
authors.forename: Nuria
authors.initials: N
authors.lastname: Ribelles
authors.forename: José
authors.initials: J
authors.lastname: Lozano
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D009154:Mutation; D018295:Neoplasms, Basal Cell / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D053555:Keratin-5; D053553:Keratin-6; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018631:ras Proteins; C117307:KRAS protein, human; C503940:KRT5 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human
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