Abstract 3556: Administration of omega-3 fatty acids and raloxifene individually and in combination to women at high risk of breast cancer: Interim feasibility data and biomarker analysis from a randomized clinical trial

The antiestrogen, Raloxifene (Ral), is an effective breast cancer chemopreventive agent. Literature data appears to support a protective role of omega-3 fatty acids (n-3FA) against mammary carcinogenesis. On the basis of their mechanisms of action, this trial tests for the first time the hypothesis that a combination of antiestrogens and n-3FA may be superior in reducing select biomarkers of breast cancer risk in women. This combination with n-3FA may also allow a lower dose of Ral to be effective with less adverse events. Healthy postmenopausal women at increased risk for breast cancer (based on breast density β25%) were randomized into five groups: 1) No intervention; 2) Ral 60 mg; 3) Ral 30 mg; 4) n-3FA (Lovaza) 4 gm; and 5) Lovaza 4 gm + Ral 30 mg for two years. While the primary endpoint of our clinical trial is a reduction in breast density, an established risk factor for breast cancer, we are also examining the effects of the individual and combined administration of Ral and n-3FA on several biomarkers thought to be potentially involved in mammary carcinogenesis. We report preliminary data on the first 46 women who complete one year of the study for feasibility, compliance, and changes in secondary endpoints related to IGF-I signaling (IGF-1, IGF-BP3), estrogen metabolism (2OHE1, 16αOH1), oxidative stress (8-OH-dG, GSH, 8-isoprostane) and inflammation (IL-6, CRP). Anthropometric measurements (including weight, BMI and waist to hip ratio) were followed at each visit. Dietary and physical activity data were monitored with food frequency and physical activity questionnaires. Plasma fatty acid analysis in the Lovaza groups were compared to the control group to ensure compliance; lipid analysis was also performed. All interventions were well tolerated with excellent compliance (96 ± 1% overall) by pill count and also supported by the expected rise at twelve months in both serum n-3FA and n-3FA/n-6FA ratio (48% and 40%, respectively) in both groups receiving Lovaza (p