Evaluation Of Pro-Apoptotic Bim Gene Loss Of Function On Lapatinib Efficacy In Patients With Metastatic Breast Cancer (Mbc) And In Her2-Amplified Cell Lines

e11590 Background: BIM is a pro-apoptotic Bcl-2 protein. Cellular BIM levels are upregulated by tyrosine kinase inhibitors (TKI) and BIM expression is correlated with TKI-induced cancer cell apoptosis. Limited studies suggest lapatinib response is correlated with BIM expression in HER2-amplified cell lines and in tumor samples from a small cohort of MBC patients. A common germline deletion polymorphism in BIM confers loss of function and has been reported to mediate resistance to TKI therapy in patients with NSCLC or CML. Methods: Using blood sample germline DNA collected from patients with HER2 positive MBC during the clinical study EGF104535 (NCT00281658), we investigated the effect of the BIM deletion polymorphism on response to lapatinib, when administered in combination with paclitaxel. In addition, the effect of BIM siRNA knockdown on lapatinib anti-proliferative activity was evaluated in three HER2-amplified breast cancer cell lines (BT474, SrBr3, and HCC1954). Results: DNA was collected from 279 o...