Abstract CT086: Omega-3 fatty acids and ERPR(-) and HER-2/neu(+) breast cancer prevention
Authors: Yee Lisa D. , Lester Joanne L. , Straka Shana R. , Woelke Sarah , Ke Jia-Yu , Shen Rulong , Yan Pearlly , Zhang Jianying , Belury Martha A. , Clinton Steven K. 
Published: July 2016

Abstract
Background: Breast cancer is a family of diseases, each with distinctive biologic behaviors and clinical outcomes. Refining therapy for specific breast cancer subtypes improves survival and limits toxicity. The application of these concepts to prevention has been limited and is a novel aspect of this clinical trial. Our pre-clinical research demonstrated that diets enriched in fish oil decreased the incidence and multiplicity of estrogen receptor negative, progesterone receptor negative (ERPR-), HER-2/neu positive (HER2+) mammary tumors in HER-2/neu transgenic mice, with decreased mammary atypia, Ki67 and COX-2 expression (Yee et al, 2005, 2012). Of interest is whether human breast cancers with poor prognostic features of negative hormone receptor status ± HER-2/neu overexpression might be uniquely responsive to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the long chain ω-3 fatty acids (FAs) found in fish oil. This study aims to determine biological changes associated with a low vs high dose of ω-3 FAs over 12 months in women at high risk for recurrent breast cancer. Doses were based on our dose finding study of ω-3 FAs in high risk women that showed superiority of ? 2.52 g EPA+DHA/day vs 0.84 g/day to increase serum and breast adipose tissue EPA+DHA content over 6 months (Yee et al, 2010). The objectives of the trial are to develop novel mammary epithelial, adipose tissue markers of exposure and response to ω-3 FAs that can be carried forward into definitive intervention trials of ω-3 FAs for breast cancer prevention.
Methods: This is a double blinded randomized trial of high dose (∼5.4 g EPA+DHA) or low dose (∼0.9 g EPA+DHA in fatty acid mix of the typical American diet) of ω-3 FAs provided in 5 capsules/day for 12 months. Cellular samples of breast epithelial and adipose tissue are obtained by fine needle aspiration (FNA) to determine the effects of ω-3 FAs on mammary tissue biomarkers of ω-3 exposure, DNA methylation patterns, and intermediate anti-carcinogenic endpoints related to inflammation. Sample size of 40 participants per arm was justified to provide at least 80% power to detect a difference of interest (e.g. 1.5 fold) for each primary endpoint (six in total) based on two-sided t test with Bonferroni adjustment for multiplicity (α = 0.05/6 = 0.008, CV = 50%). This study focuses on women survivors of high risk breast cancer subtypes, namely triple negative or ERPR(-),HER2(+) disease, who are currently without long term adjuvant options. Eligibility criteria include prior diagnosis of ERPR(-) Stage 0 to III breast cancer, ?5 years from completion of standard therapy. Ineligibility criteria include current malignancy, inability to undergo breast FNA, chronic use of ω-3 FAs/fish oil, NSAIDs or full dose aspirin. The trial opened in September 2014 with first enrollment 9/16/14. 43% of planned participants have enrolled as of January 2016. The trial is continuing as planned. This study is registered at ClinicalTrials.gov (NCT02295059) and supported by the National Cancer Institute (1R01CA164019-01A1).
Citation Format: Lisa D. Yee, Joanne L. Lester, Shana R. Straka, Sarah Woelke, Jia-Yu Ke, Rulong Shen, Pearlly Yan, Jianying Zhang, Martha A. Belury, Steven K. Clinton. Omega-3 fatty acids and ERPR(-) and HER-2/neu(+) breast cancer prevention. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT086.