Effect of omega-3 fatty acids alone and in combination with raloxifene on biomarkers of breast cancer risk in postmenopausal healthy women at high risk.

Abstract

e11036 Background: Prevention represents the most effective approach to reducing mortality from breast cancer. To translate our preclinical findings in this regard we are conducting a 2-year randomized clinical trial in healthy postmenopausal women with increased breast cancer risk based on breast density (>25%). Methods: We are studying the effects of omega-3 fatty acids (FA) alone and in combination with raloxifene on several biomarkers including those of inflammation (CRP, IL-6), estrogen metabolism (2-hydroxyestrone, 16-α-hydroxyestrone), oxidative status (glutathione [GSH]), IGF-1 signaling (IGF-1, IGFBP-3) and plasma FA. Our study consists of 5 groups: (1) no intervention; (2) raloxifene 60mg; (3) raloxifene 30mg; (4) omega-3-acid ethyl esters (Lovaza) 4g; (5) raloxifene 30mg + Lovaza 4g. We report here preliminary findings from the first 46 women after 1 year. Results: Raloxifene reduced serum IGF-1 (12% in Group 3 and 20% in Group 2) compared to control (Group 1) in a dose-dependent fashion (p=0.005) while Lovaza alone had no effect (Group 4). The effect of Lovaza in combination with raloxifene (Group 5) was comparable to raloxifene alone (Group 3). Serum CRP, IL-6, IGFBP-3, 2-hydroxyestrone and 16-α-hydroxyestrone were unchanged in all groups. Blood GSH showed an increasing trend with Lovaza, but was not significant (p=0.07). Plasma FA changes by Lovaza included 2.5-fold increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), an increase in the omega-3/omega-6 ratio (0.12 + 0.01 at baseline to 0.30 + 0.06 at 1 year) and decreased arachidonic acid (AA) (0.54 + 0.05 μmol/mL at baseline to 0.35 + 0.02 at 1 year) (p<0.05). Conclusions: Our results support the role of decreased IGF-1 levels as a potential mechanism of breast cancer risk reduction by raloxifene which may not be driven by effects on IGFBP-3. The Lovaza-induced increase in omega-3 FA levels and decrease in AA are consistent with our preclinical findings. An increased trend of blood GSH by Lovaza may indicate enhanced antioxidant activity. Collectively, these results suggest that the combination of omega-3 FA and raloxifene may be a promising approach for impacting critical targets for breast cancer prevention.