Abstract P4-10-01: High dose omega-3 fatty acid supplementation modulates breast tissue biomarkers in post-menopausal women at high risk for development of breast cancer

Abstract

Abstract Background: We conducted a pilot study of high dose omega-3 fatty acid (FA) supplementation in post-menopausal women to determine if risk biomarkers for breast cancer in benign breast tissue sampled by random peri-areolar aspiration (RPFNA) could be favorably modulated and to acquire preliminary data on possible mechanism of action. Methods: 35 post-menopausal women at increased risk for breast cancer were accrued to a trial of 6-month intervention with 4 g daily of omega-3-acid ethyl esters [1.86 g eicosapentaenoic acid (EPA), 1.5 g docosahexaenoic acid (DHA)]. Subjects had RPFNA performed pre- and post-intervention and specimens evaluated for cytomorphology and proliferation (Ki-67). FA composition was determined in plasma, red blood cells, and RPFNA specimens. Additional specimens were frozen for assessment of hormones, a panel of 11 adipokines and cytokines by Luminex, and gene expression. Results: 34 subjects completed study with specimens evaluable for change in biomarkers. The ratio of (EPA+DHA):Arachidonic Acid (AA) levels in erythrocyte phospholipid increased significantly by a median of 2.7-fold. Although there was a significant decrease in blood EPA+DHA between discontinuation at 6 months and 2 weeks later when RPFNA was performed, all ratios were above the baseline value (median 1.6-fold). There was favorable but not statistically significant modulation for cytologic evidence of atypia (53% at baseline to 41% at off-study). However, favorable modulation was exhibited for Masood score (medians of 15 to 14; p = 0.014), number of epithelial cells recovered (p = 0.019) and Ki-67 expression (medians of 1.7% to 0.75%, p = 0.036, despite 8 subjects having no Ki-67 expression at baseline). Luminex assay of serum indicated a statistically significant increase (p = 0.003) for adiponectin and decrease (p = 0.016) for TNF-alpha between baseline and off-study. For RPFNA specimens, there was a significant decrease (P = 0.001) in MCP-1 levels adjusted for protein content. By ELISA, serum high molecular weight adiponection increased (p = 0.046) and molar ratio of IGF-1:IGFBP3 decreased (p = 0.006). Note that all analyses were exploratory and without correction for multiple analyses. Conclusion: Favorable modulation of a variety of blood and tissue risk biomarkers, including cytomorphology and proliferation, along with good tolerability suggests that high dose omega-3 FA esters should be tested further in a placebo-controlled trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-10-01.