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

Carol J. Fabian, Bruce F. Kimler, Teresa A. Phillips, Jessica A. Box, 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

    23 Scopus citations

    Abstract

    Higher intakes of the omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) have been variably associated with reduced risk of premenopausal breast cancer. The purpose of this pilot trial was to assess feasibility and explore the effects of high-dose EPA and DHA on blood and benign breast tissue risk biomarkers before design of a placebo-controlled phase IIB trial. Premenopausal women with evidence of hyperplasia-Atypia by baseline random periareolar fine needle aspiration were given 1860 mg of EPA + 1500mgofDHAethyl esters daily for 6 months. Blood and benign breast tissue were sampled during the same menstrual cycle phase prestudy and a median of 3 weeks after last dose. Additional blood was obtained within 24 hours of last dose. Feasibility, which was predefined as 50% uptake, 85% retention, and 70% compliance, was demonstrated with 46% uptake, 94% completion, and 85% compliance. Cytologic atypia decreased from 77% to 38% (P = 0.002), and Ki-67 from a median of 2.1% to 1.0% (P = 0.021) with an increase in the ratio of EPA + DHA to AA in erythrocyte phospholipids but no change in blood hormones, adipokines, or cytokines. Exploratory breast proteomics assessment showed decreases in several proteins involved in hormone and cytokine signaling with mixed effects on those in the AKT/ mTORpathways. Further investigation of EPA plusDHAfor breast cancer prevention in a placebo-controlled trial in premenopausal women is warranted.

    Original languageEnglish (US)
    Pages (from-to)912-921
    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., Box, J. A., 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 premenopausal women. Cancer Prevention Research, 8(10), 912-921. https://doi.org/10.1158/1940-6207.CAPR-14-0335