Abstract 158: Modulation of breast tissue biomarkers by high dose omega-3 fatty acid supplementation in women at high risk for development of breast cancer.
Authors: Fabian Carol J. , Kimler Bruce F. , Zalles Carola M. , Metheny Trina , Box Jessica A. , Nydegger Jennifer L. , Phillips Teresa A. , Hidaka Brandon H. , Carlson Susan E. 
Published: August 2014

Background. Previously, we had observed that women at high risk for development of breast cancer were more likely to exhibit cytologic hyperplasia with atypia in specimens acquired by random periareolar fine needle aspiration (RPFNA) if they had low intake and/or low plasma, red blood cell, or breast tissue levels of omega-3 relative to omega-6 fatty acids. We evaluated the effect of high dose omega-3 supplementation on breast tissue markers in two parallel pilot studies, one of pre-menopausal and one of post-menopausal women. Methods. 36 pre-menopausal and 35 post-menopausal women at high risk for breast cancer had breast tissue harvested by RPFNA before and after a 6-month intervention with 4 g daily of omega-3-acid ehyl esters [1.86 g eicosapentaenoic acid (EPA), 1.5 g docosahexaenoic acid (DHA)]. Premenopausal women were aspirated in the follicular phase of the menstrual cycle. Specimens were evaluated for tissue risk biomarkers including cytomorphology, proliferation (Ki-67). Fatty acid composition was determined in plasma, red blood cells, and breast RPFNA specimens. Additional blood and frozen breast tissue was reserved for assessment of hormones, adipokines, cytokines and gene expression. Results. To date, only two of the 71 subjects have discontinued the study early, while 50 subjects have completed study and are evaluable for modulation of tissue biomarkers. Grade 2 or greater gastrointestinal side effects have been reported by only seven subjects. Favorable modulation was observed for cytologic evidence of atypia (70% to 44%; p=0.012), Masood score (medians of 15 to 14; p=0.001), number of epithelial cells recovered (p=0.002), and Ki-67 expression (p=0.059 if all subjects are included even if they did not exhibit Ki-67 staining at baseline, medians of 1.7% to 0.8%; or p=0.001 for 27 women with baseline Ki-67 &gt;1.5%, medians of 3.2% to 1.4%). Modulation was more prevalent (and was statistically significant for all variables) in pre-menopausal women than in post-menopausal women. Fatty acid assessment, adipokine and cytokine assays are batched to minimize variability and all results are not yet available. Preliminary results indicate that the ratio of omega-3:omega-6 fatty acids increased in erythrocytes and plasma by two-fold after 6 months of the high dose omega-3 fatty acid intervention. Conclusion. High dose supplementation with omega-3 fatty acids is well-tolerated in healthy women at high risk for development of breast cancer and was associated with favorable modulation of the tissue risk biomarkers of cytologic atypia and proliferation. This strategy will be explored further as a promising intervention that may reduce risk for development of breast cancer. Supported in part by funding from the Breast Cancer Research Foundation and the Kansas Bioscience Authority. Study agent was provided by GlaxoSmithKline.

Citation Format: Carol J. Fabian, Bruce F. Kimler, Carola M. Zalles, Trina Metheny, Jessica A. Box, Jennifer L. Nydegger, Teresa A. Phillips, Brandon H. Hidaka, Susan E. Carlson. Modulation of breast tissue biomarkers by high dose omega-3 fatty acid supplementation in women at high risk for development of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 158. doi:10.1158/1538-7445.AM2013-158