Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Mutational analysis of the <it>KRAS </it>gene has recently been established as a complementary <it>in vitro </it>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 <it>KRAS </it>might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although <it>KRAS </it>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 <it>KRAS </it>in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.</p> <p>Methods</p> <p>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. <it>KRAS </it>mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type <it>KRAS </it>or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.</p> <p>Results</p> <p>We found no evidence of <it>KRAS </it>oncogenic mutations in all analyzed tumors.</p> <p>Conclusions</p> <p>This study indicates that <it>KRAS </it>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.</p