Abstract 3486: Interaction of flaxseed oil with trastuzumab in HER2 overexpressing human breast tumors (BT-474)

BACKGROUND: Trastuzumab (TRAS) is a first line therapy for breast tumors that overexpress the human epidermal growth factor receptor 2 (HER2) but tumors develop resistance within one year of treatment. Flaxseed oil (FO) rich in n-3 fatty acid alpha linolenic acid (ALA) has been shown to reduce HER2 expression and signalling in estrogen receptor positive human breast tumors. Our objective was to determine whether combining dietary FO with TRAS treatment will enhance TRAS effectiveness in reducing tumor growth. METHODS: Ovariectomized mice with established HER2 overxpressing tumors (BT-474) and estrogen pellet implant were fed the basal diet (BD) (control) or treated with TRAS (1 or 2.5mg/kg body weight) and fed either the BD or BD supplemented with 4% FO for 4 weeks. Palpable tumor area was measured weekly. After animal sacrifice, excised tumors were analyzed using immunohistochemistry for cell proliferation (Ki-67) and apoptosis and using Western blot analysis for HER2, MAPK and Akt. RESULTS: Tumors in the control, TRAS1, TRAS2.5, and TRAS1+FO, had palpable tumor areas that significantly increased (p