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

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.We found no evidence of KRAS oncogenic mutations in all analyzed tumors.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.Breast cancer is a complex and heterogeneous disease that includes tumors of variable prognosis and clinical response to treatments [1]. Standard breast tumor classification has long relied on morphological and anatomical criteria such as tumor size and extension (TNM staging), histopathological features (tumor grade) and expression of protein markers such as the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) oncogene [1,2]. While these parameters may correlate well with survival in some patients, their value as prognostic and predictive factors is limited given the fact that patients with similar tumors often have a different clinical progression and treatment response [1,2]. The existence of such differences in the clinical outcome of breast cancer patients can be explained by intrinsic tumor variability at the molecular level [3-7]. In two landmark studies, Perou et al. and Sorlie et al. [3,5] identified five distinct "intrinsic" subtypes of breast cancer by hierarchical cluster analysis of microarray gene expression data: luminal A and luminal B [both estroge