Abstract Title:

Modulation of Breast Cancer Risk Biomarkers by High Dose Omega-3 Fatty Acids: Phase II Pilot Study in Post-menopausal Women.

Abstract Source:

Cancer Prev Res (Phila). 2015 Aug 14. Epub 2015 Aug 14. PMID: 26276744

Abstract Author(s):

Carol J Fabian, Bruce F Kimler, Teresa A Phillips, Jennifer L Nydegger, Amy L Kreutzjans, Susan E Carlson, Brandon H Hidaka, Trina Metheny, Carola M Zalles, Gordon B Mills, Kandy R Powers, Debra K Sullivan, Brian K Petroff, Whitney L Hensing, Brooke L Fridley, Stephen D Hursting

Article Affiliation:

Carol J Fabian

Abstract:

Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high dose EPA + DHA in post-menopausal women to assess feasibility prior to initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1820 mg EPA +1530 mg DHA ethyl esters daily for 6 months. Blood and breast tissue was sampled at baseline and study conclusion for exploratory biomarker assessment, with p values uncorrected for multiple comparisons. Feasibility was pre-defined as 50% uptake, 80% completion and 70% compliance. Trial uptake by 35 study entrants from 54 eligible women was 65%, with 97% completion and 97% compliance. Favorable modulation was suggested for serum adiponectin (p=0.0027), TNF-alpha (p=0.016), HOMA 2B measure of pancreatic beta cell function (p=0.0048) and bioavailable estradiol (p=0.039). Benign breast tissue Ki-67 (p=0.036), macrophage chemoattractant protein-1 (p=0.033), cytomorphology index score (p=0.014), and percent mammographic density (p=0.036) were decreased with favorable effects in a proteomics array for several proteins associated with mitogen signaling and cell cycle arrest; but no obvious overall effect on proteins downstream of mTOR. Although favorable risk biomarker modulation will need to be confirmed in a placebo-controlled trial, we have demonstrated feasibility for development of high dose EPA and DHA ethyl esters for primary prevention of breast cancer.

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