Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women.
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.
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas. cfabian@kumc.edu.
Carol J
CJ
Fabian
Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas.
Bruce F
BF
Kimler
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Teresa A
TA
Phillips
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Jennifer L
JL
Nydegger
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Amy L
AL
Kreutzjans
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
Susan E
SE
Carlson
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
Brandon H
BH
Hidaka
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Trina
T
Metheny
Mercy Hospital, Miami, Florida.
Carola M
CM
Zalles
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Gordon B
GB
Mills
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Kandy R
KR
Powers
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
Debra K
DK
Sullivan
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Brian K
BK
Petroff
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Whitney L
WL
Hensing
Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas.
Brooke L
BL
Fridley
Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
Stephen D
SD
Hursting
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002855:Chromatography, Thin Layer; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000097:blood* / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D008875:Middle Aged; D010865:Pilot Projects; D017698:Postmenopause; D011230:Precancerous Conditions / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012107:Research Design; D012307:Risk Factors
D014408:Biomarkers, Tumor; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor