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.

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.

• Authors: C Signori, C DuBrock, J P Richie, B Prokopczyk, L M Demers, C Hamilton, T J Hartman, J Liao, K El-Bayoumy, A Manni
• Journal: European journal of clinical nutrition (Eur J Clin Nutr) Vol. 66 Issue 8 Pg. 878-84 (Aug 2012) ISSN: 1476-5640 [Electronic] England
• PMID: 22669332 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Adult
• Aged
• Biomarkers (blood, urine)
• Breast Neoplasms (physiopathology, prevention & control)
• C-Reactive Protein (analysis, metabolism)
• Docosahexaenoic Acids
• Dose-Response Relationship, Drug
• Drug Combinations
• Eicosapentaenoic Acid
• Endpoint Determination
• Estrogen Antagonists (administration & dosage)
• Fatty Acids, Omega-3 (administration & dosage, 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