Development of Biologically Based Therapies for Basal-Like Tumors

The basal-like subtype of breast cancer is both estrogen receptor and HER2 negative and therefore is not effectively treated by hormonal therapy or trastuzamab. The purpose of this research is to identify treatment options for this subset of breast cancer patients. Breast cell lines of basal-like and luminal origin were treated with five different chemotherapeutics to determine sensitivity levels. The basal-like cell lines were more sensitive to carboplatin than luminal lines. Next, we focused on identifying a biologic therapy targeting the basal-like subtype. HER1EGFR is expressed in approximately 50 of the basal-like tumors while not expressed in the luminal tumors. The basal-like cell lines showed an increased sensitivity to several EGFR inhibitors compared to the luminal lines. Combinations of two EGFR were synergistic with carboplatin. This work is support for a clinical trial at UNO, which will treat basal-like breast cancer patients with a HER1 inhibitor with or without carboplatin. An EGFR activation signature was identified and shown to predict poor outcome in two breast tumor data sets. In basal-like tumors, there may be many mechanisms for activation of this pathway but many appear to be downstream of EGFR in the RAS-MEK-ERK pathway. This work shows that basal-like may need to be further stratified to identify successful treatment regimens.