Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women
Autor: | Brandon H. Hidaka, Brian K. Petroff, Brooke L. Fridley, Bruce F. Kimler, Amy L. Kreutzjans, Whitney L. Hensing, Debra K. Sullivan, Trina Metheny, Jennifer L. Nydegger, Gordon B. Mills, Carol J. Fabian, Kandy R. Powers, Teresa A. Phillips, Carola M. Zalles, Stephen D. Hursting, Susan E. Carlson |
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Rok vydání: | 2015 |
Předmět: |
Adult
Cancer Research medicine.medical_specialty Pathology Docosahexaenoic Acids Breast Neoplasms Pilot Projects Real-Time Polymerase Chain Reaction Gastroenterology Article chemistry.chemical_compound Breast cancer Risk Factors Internal medicine Fatty Acids Omega-3 Biomarkers Tumor Humans Medicine Aged Hyperplasia business.industry Middle Aged medicine.disease Eicosapentaenoic acid Postmenopause Drug Combinations Eicosapentaenoic Acid Oncology chemistry Research Design Docosahexaenoic acid Feasibility Studies Biomarker (medicine) lipids (amino acids peptides and proteins) Female Arachidonic acid Chromatography Thin Layer business Precancerous Conditions Random Periareolar Fine-Needle Aspiration Hormone |
Zdroj: | Cancer Prevention Research. 8:922-931 |
ISSN: | 1940-6215 1940-6207 |
DOI: | 10.1158/1940-6207.capr-14-0336 |
Popis: | 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), TNFα (P = 0.016), HOMA 2B measure of pancreatic β 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. Cancer Prev Res; 8(10); 922–31. ©2015 AACR. See related article, p. 912. |
Databáze: | OpenAIRE |
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