Abstract
1099 Background: An urgent problem in breast cancer treatment is the identification and validation of a targeted therapy for triple-negative breast cancer (TNBC), ie, breast cancer negative for ER, PR and HER2. Neratinib is a low molecular weight irreversible pan-HER inhibitor that selectively targets the tyrosine kinase activity of EGFR, HER2 and HER4. To-date, neratinib has been exclusively investigated in HER2-positive tumors. However, as neratinib also targets EGFR expression, we hypothesised that it may also have clinical efficacy in TNBC. Methods: The anti-proliferative effects of neratinib were investigated in 14 TNBC cell lines. To identify potential biomarkers of response, we examined the expression of baseline EGFR, HER2, HER3 and HER4 using reverse phase protein array (RPPA) analysis and flow cytometry analysis. Results: IC50 values for neratinib across the 14 TNBC cell lines ranged from 0.06 µM to 1.9 µM. However, basal A-type cells were significantly more sensitive to neratinib than basal B-t...
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