Change in Blood and Benign Breast Biomarkers in Women Undergoing a Weight-Loss Intervention Randomized to High-Dose ω-3 Fatty Acids versus Placebo

Carol J Fabian, Christie A Befort, Teresa A Phillips, Jennifer L Nydegger, Amy L Kreutzjans, Kandy R Powers, Trina Metheny, Jennifer R Klemp, Susan E Carlson, Debra K Sullivan, Carola M Zalles, Erin D Giles, Stephen D Hursting, Jinxiang Hu, Bruce F Kimler, Carol J Fabian, Christie A Befort, Teresa A Phillips, Jennifer L Nydegger, Amy L Kreutzjans, Kandy R Powers, Trina Metheny, Jennifer R Klemp, Susan E Carlson, Debra K Sullivan, Carola M Zalles, Erin D Giles, Stephen D Hursting, Jinxiang Hu, Bruce F Kimler

Abstract

The inflammation-resolving and insulin-sensitizing properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have potential to augment effects of weight loss on breast cancer risk. In a feasibility study, 46 peri/postmenopausal women at increased risk for breast cancer with a body mass index (BMI) of 28 kg/m2 or greater were randomized to 3.25 g/day combined EPA and DHA (ω-3-FA) or placebo concomitantly with initiation of a weight-loss intervention. Forty-five women started the intervention. Study discontinuation for women randomized to ω-3-FA and initiating the weight-loss intervention was 9% at 6 months and thus satisfied our main endpoint, which was feasibility. Between baseline and 6 months significant change (P < 0.05) was observed in 12 of 25 serum metabolic markers associated with breast cancer risk for women randomized to ω-3-FA, but only four for those randomized to placebo. Weight loss (median of 10% for trial initiators and 12% for the 42 completing 6 months) had a significant impact on biomarker modulation. Median loss was similar for placebo (-11%) and ω-3-FA (-13%). No significant change between ω-3-FA and placebo was observed for individual biomarkers, likely due to sample size and effect of weight loss. Women randomized to ω-3-FA exhibiting more than 10% weight loss at 6 months showed greatest biomarker improvement including 6- and 12-month serum adiponectin, insulin, omentin, and C-reactive protein (CRP), and 12-month tissue adiponectin. Given the importance of a favorable adipokine profile in countering the prooncogenic effects of obesity, further evaluation of high-dose ω-3-FA during a weight-loss intervention in obese high-risk women should be considered. PREVENTION RELEVANCE: This study examines biomarkers of response that may be modulated by omega-3 fatty acids when combined with a weight-loss intervention. While focused on obese, postmenopausal women at high risk for development of breast cancer, the findings are applicable to other cancers studied in clinical prevention trials.

Conflict of interest statement

C.J. Fabian, C.A. Befort, T.A. Phillips, J.L. Nydegger, A.L. Kreutzjans, K.R. Powers, T. Metheny, J.R. Klemp, S.E. Carlson, D.K. Sullivan, J. Hu, and B.F. Kimler report grants to their institution during the conduct of the study from Breast Cancer Research Foundation, NIH, and Morris Family Foundation; non-financial support from DSM Nutritional Products, Inc. No disclosures were reported by the other authors.

©2021 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Consort diagram.
Figure 2.
Figure 2.
Number of serum biomarkers modulated at 6 months within each of the four groups; ω-3 versus placebo × weight loss 10%.

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