Influence of obesity on breast density reduction by omega-3 fatty acids: Evidence from a randomized clinical trial.
Cancer Prev Res (Phila). 2015 Dec 29. Epub 2015 Dec 29. PMID: 26714774
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. Pre-clinical 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 two-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 1) No treatment, Control; 2) Raloxifene 60 mg; 3) Raloxifene 30 mg; 4) n-3FA Lovaza 4 gm and 5) Lovaza 4 gm plus Raloxifene 30 mg. The two-year change in BD, a validated biomarker of breast cancer risk was the primary endpoint of the study. In subset analysis, we tested the pre-specified 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.