title: Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Premenopausal Women.
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 + 1500 mg of DHA ethyl 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/mTOR pathways. Further investigation of EPA plus DHA for breast cancer prevention in a placebo-controlled trial in premenopausal women is warranted.
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas. cfabian@kumc.edu.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
authors.affiliation: Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Phillips
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Box
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kreutzjans
authors.affiliation: Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Carlson
authors.affiliation: Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Hidaka
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Trina
authors.initials: T
authors.lastname: Metheny
authors.affiliation: Mercy Hospital, Miami, Florida.
authors.forename: Carola M
authors.initials: CM
authors.lastname: Zalles
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Kandy R
authors.initials: KR
authors.lastname: Powers
authors.affiliation: Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Debra K
authors.initials: DK
authors.lastname: Sullivan
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Petroff
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Hensing
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000517:prevention & control*; D002855:Chromatography, Thin Layer; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000473:pathology; D017697:Premenopause; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D019394:Ki-67 Antigen; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor