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.
OBJECTIVE
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.


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.


CONCLUSIONS
The combination of Lovaza and Ral is a feasible strategy that may be recommended in future breast cancer chemoprevention trials.
Department of Medicine, Hershey, PA, USA.
C
C
Signori
C
C
DuBrock
J P
JP
Richie
B
B
Prokopczyk
L M
LM
Demers
C
C
Hamilton
T J
TJ
Hartman
J
J
Liao
K
K
El-Bayoumy
A
A
Manni
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D001943:Breast Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D004281:Docosahexaenoic Acids; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid; D023381:Endpoint Determination; D004965:Estrogen Antagonists / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000627:therapeutic use; D005240:Feasibility Studies; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016014:Linear Models; D015227:Lipid Peroxidation / Q000187:drug effects; D008875:Middle Aged; D009043:Motor Activity; D018384:Oxidative Stress / Q000187:drug effects; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage; D015398:Signal Transduction
D015415:Biomarkers; D004338:Drug Combinations; D004965:Estrogen Antagonists; D015525:Fatty Acids, Omega-3; D018972:Insulin-Like Growth Factor Binding Protein 3; D020845:Selective Estrogen Receptor Modulators; D004281:Docosahexaenoic Acids; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid; C405603:Omacor