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Background Lapatinib has been used in combination with capecitabine or paclitaxeltotreatpatients with progressive HER2-overexpressing metastatic breast cancer (MBC).Unfortunately, an increased incidence of hepatotoxicityhad been reportedinthe combinational therapy.The aim of this study was to investigate the potential mechanisms of this combinational therapy.Methods The incidence of hepatotoxicity was evaluated in patients and Swiss mice treated with combination of lapatinib and paclitaxel or doxorubicin.