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Lipids and cardiovascular/metabolic health

Administration of omega-3 fatty acids and Raloxifene to women at high risk of breast cancer: interim feasibility and biomarkers analysis from a clinical trial

European Journal of Clinical Nutrition volume 66, pages 878–884 (2012)Cite this article

Subjects

Abstract

Background/Objectives:

The antiestrogen, Raloxifene (Ral) is an effective breast cancer chemopreventive agent. Omega-3 fatty acids (n-3FA) may inhibit mammary carcinogenesis. On the basis of their mechanisms of action, we test the hypothesis that a combination of n-3FA and Ral may be superior in reducing select biomarkers of breast cancer risk in women.

Subjects/Methods:

Postmenopausal women at increased risk for breast cancer (breast density ⩾25%) were randomized to: (1) no intervention; (2) Ral 60 mg; (3) Ral 30 mg; (4) n-3FA (Lovaza) 4 g and (5) Lovaza 4 g+Ral 30 mg for 2 years. Reduction in breast density is the primary end point of the study. We report preliminary data on feasibility, compliance and changes in secondary end points related to IGF-I signaling, estrogen metabolism, oxidative stress and inflammation in the first group of 46 women who completed 1 year of the study.

Results:

All interventions were well tolerated with excellent compliance (96±1% overall) by pill count and also supported by the expected rise in both serum n-3FA and n-3FA/Omega-6 fatty acids (n-6FA) ratio in women randomized to groups 4 and 5 (P<0.05). Lovaza decreased serum triglycerides and increased high-density lipoprotein (HDL) cholesterol compared with control (P<0.05 for both). Ral reduced serum IGF-1 in a dose-dependent manner (P<0.05) while Lovaza did not. Lovaza had no effect on IGF-1 or IGFBP-3. None of the other biomarkers were affected by our treatment.

Conclusion:

The combination of Lovaza and Ral is a feasible strategy that may be recommended in future breast cancer chemoprevention trials.

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Acknowledgements

We thank Glaxo Smith Kline and Eli-Lilly for their generous supply of Lovaza and Raloxifene, respectively. This work was supported by Susan G Komen for the Cure Grant no. KG081632.

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Authors and Affiliations

  1. Department of Medicine, Hershey, PA, USA

    C Signori, C DuBrock & A Manni

  2. Department of Public Health Sciences, Hershey, PA, USA

    J P Richie & J Liao

  3. Department of Pharmacology, Hershey, PA, USA

    B Prokopczyk

  4. Department of Pathology, Hershey, PA, USA

    L M Demers & C Hamilton

  5. Department of Nutrition, University Park, PA, USA

    T J Hartman

  6. Department of Biochemistry and Molecular Biology, Hershey, PA, USA

    K El-Bayoumy

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  1. C Signori
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Correspondence to A Manni.

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Signori, C., DuBrock, C., Richie, J. et al. Administration of omega-3 fatty acids and Raloxifene to women at high risk of breast cancer: interim feasibility and biomarkers analysis from a clinical trial. Eur J Clin Nutr 66, 878–884 (2012). https://doi.org/10.1038/ejcn.2012.60

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