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.

Collagen and fibronectin: threads linking obesity and breast cancer

“…ω-3 PUFAs have recently been shown to ameliorate liver fibrosis by promoting YAP/TAZ degradation (14) and it is intriguing to speculate that beneficial effects of ω-3 PUFAs on breast cancers of obese individuals could be mediated via the inhibition of YAP/TAZ activity. This would be in keeping with results of a recent randomized clinical trial showing that ω-3 PUFAs decrease breast density in obese, but not overweight or normal weight postmenopausal women (15).…”

The Conundrum of Omega-3 Fatty Acids in Cancer Prevention Studies: Which One? How Much? What Biomarkers?

“…In preclinical studies, EPA appears to have higher proportional absorption into membranes of ER þ MCF-7 cells than DHA, whereas DHA may have greater proportional absorption in triple-negative cell lines and may be superior in reducing EGFR signaling due to better lipid raft absorption and spatial receptor disruption (8). Given the promising preclinical data in ER À cell lines and early reports that DHA may be superior to EPA in reducing inflammation, some early-phase breast cancer prevention studies, such as that reported in this issue, have used DHA alone, whereas others following more traditional epidemiologic leads have used combinations of EPA and DHA (9)(10)(11). A recently reported clinical trial in a relatively homogeneous cohort with abdominal obesity and baseline CRP evidence of inflammation found little difference in whole blood inflammatory gene expression between 2.7 g/day of EPA Figure 1.…”

Phytotherapy and Nutritional Supplements on Breast Cancer

“…Patterson and collaborators did not associate EPA and DHA intake from fish oil supplements with breast cancer outcomes [ 230 ]. Sandhu et al found an increased effect of protective omega-3 fatty acid supplementation in higher body mass index women [ 244 ].…”