Modulation of breast cancer risk biomarkers by high-dose omega-3 fatty acids: Phase II pilot study in postmenopausal women

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

    Research output: Contribution to journalArticle

    13 Scopus citations

    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 postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, with P values uncorrected for multiple comparisons. Feasibility was predefined 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), TNFa (P = 0.016), HOMA 2B measure of pancreatic b 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-doseEPA andDHAethyl esters for primary prevention of breast cancer.

    Original languageEnglish (US)
    Pages (from-to)922-931
    Number of pages10
    JournalCancer Prevention Research
    Volume8
    Issue number10
    DOIs
    StatePublished - Oct 1 2015

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Fabian, C. J., Kimler, B. F., Phillips, T. A., Nydegger, J. L., Kreutzjans, A. L., Carlson, S. E., Hidaka, B. H., Metheny, T., Zalles, C. M., Mills, G. B., Powers, K. R., Sullivan, D. K., Petroff, B. K., Hensing, W. L., Fridley, B. L., & Hursting, S. D. (2015). Modulation of breast cancer risk biomarkers by high-dose omega-3 fatty acids: Phase II pilot study in postmenopausal women. Cancer Prevention Research, 8(10), 922-931. https://doi.org/10.1158/1940-6207.CAPR-14-0336