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. 2012 Aug;66(8):878-84. doi: 10.1038/ejcn.2012.60. Epub 2012 Jun 6.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Biomarkers / urine
  • Breast Neoplasms / physiopathology
  • Breast Neoplasms / prevention & control*
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Docosahexaenoic Acids
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Eicosapentaenoic Acid
  • Endpoint Determination
  • Estrogen Antagonists / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / therapeutic use
  • Feasibility Studies
  • Feeding Behavior*
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Linear Models
  • Lipid Peroxidation / drug effects
  • Middle Aged
  • Motor Activity
  • Oxidative Stress / drug effects
  • Postmenopause
  • Raloxifene Hydrochloride / administration & dosage*
  • Risk Factors
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Signal Transduction


  • Biomarkers
  • Drug Combinations
  • Estrogen Antagonists
  • Fatty Acids, Omega-3
  • Insulin-Like Growth Factor Binding Protein 3
  • Selective Estrogen Receptor Modulators
  • Docosahexaenoic Acids
  • Raloxifene Hydrochloride
  • Insulin-Like Growth Factor I
  • C-Reactive Protein
  • Eicosapentaenoic Acid
  • Omacor