title: Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.
abstract: Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration.
authors.affiliation: Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Narinder
authors.initials: N
authors.lastname: Sandhu
authors.affiliation: Department of Radiology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Susann E
authors.initials: SE
authors.lastname: Schetter
authors.affiliation: Department of Public Health Sciences, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Jason
authors.initials: J
authors.lastname: Liao
authors.affiliation: Rollins School of Public Health and Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Terryl J
authors.initials: TJ
authors.lastname: Hartman
authors.affiliation: Department of Pharmacology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors.forename: John
authors.initials: J
authors.lastname: McGinley
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Thompson
authors.affiliation: Department of Pharmacology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Prokopczyk
authors.affiliation: Penn State Hershey Cancer Center.
authors.forename: Cynthia
authors.initials: C
authors.lastname: DuBrock
authors.affiliation: Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Carina
authors.initials: C
authors.lastname: Signori
authors.affiliation: Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hamilton
authors.affiliation: Department of Public Health Sciences, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Ana
authors.initials: A
authors.lastname: Calcagnotto
authors.affiliation: Department of Pharmacology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Neil
authors.initials: N
authors.lastname: Trushin
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Cesar
authors.initials: C
authors.lastname: Aliaga
authors.affiliation: Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Demers
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
authors.affiliation: Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. amanni@hmc.psu.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manni
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001940:Breast / Q000000981:diagnostic imaging / Q000502:physiology; D000071060:Breast Density; D001943:Breast Neoplasms / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004281:Docosahexaenoic Acids; D020849:Raloxifene Hydrochloride; D015118:Eicosapentaenoic Acid; C405603:Omacor