Transcription profiling of human breast carcinoma tissues representing 930 patients with 17.4 years mean follow-up, basal cytokeratin expression was associated with decreased disease-specific survival

Expression profiling studies have classified breast carcinomas into luminal, normal breast-like, HER2 expressing and basal-like groups, with the latter two associated with poor outcomes. This study's objectives were to define an immunohistochemical profile that identifies basal-like tumors, to identify the presence of potential drug targets, and to determine the prognostic significance of the basal-like immunophenotype in a large series with long-term follow-up. On a panel of 21 breast tumors with basal-like expression profiles, we determined that this subtype was immunohistochemically negative for estrogen receptor and HER2, but positive for basal cytokeratins, HER1 and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4 years mean follow-up, basal cytokeratin expression was associated with decreased disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (vs. 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers, but did not influence prognosis. A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors and suggests candidate drugs for therapies targeting HER1 or c-KIT.