Preclinical studies with neratinib in triple-negative breast cancer.

1054 Background: Currently, one of the most urgent problems in breast cancer therapeutics is the validation of targeted therapy for triple-negative breast cancer (TNBC). Neratinib is an irreversible small molecule inhibitor that targets the kinase activity of EGFR, HER2 and HER4. As one of these targets, EGFR, is expressed at high levels in a subset of TNBC, we hypothesised that neratinib is a potential treatment for at least some patients with TNBC. Methods: The antiproliferative effects of neratinib were investigated in a panel of 35 breast cancer cells lines including 9 luminal, 12 HER2-positive and 14 triple-negative (TN). Baseline levels of total HER proteins were determined using flow cytometry. Results: IC50 values for neratinib across the panel of breast cancer cell lines ranged from < 0.001 - 1.9 µM. HER2-positive cell lines were significantly more sensitive to neratinib than HER2-negative cells (p = 0.008, Student’s t-test). For the 14 TN cell lines, IC50 values ranged from 0.03 – 1.9 µM. TN cel...