ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition

Yee, Lisa D.; Lester, Joanne; Cole, Rachel M.; Richardson, J. R.; Hsu, Jason C.; Li, Yan; Lehman, Amy; Belury, Martha A.; Clinton, Steven K.

doi:10.3945/ajcn.2009.29036

Cited by 82 publications

(83 citation statements)

References 33 publications

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“…These results indicate excellent compliance of our subjects with their treatment assignments for a period up to 1 year. The increase in serum n-3FA and the n-3FA/n-6FA ratio was comparable to that reported by Yee et al, 15 in their dose-response study with Lovaza administered to high-risk women (premenopausal and postmenopausal) for a 6-month duration. Since our study included a control group, we were able to exclude the possibility of 'contamination' (that is, women taking n-3FA supplements out of protocol).…”

Section: Discussionsupporting

confidence: 89%

“…This is an important issue since n-3FA preparations are readily available to the general public and are appealing in view of their advertised health benefits. Yee et al 15 observed that a higher serum baseline of DHA and BMI was significantly associated with a lower incremental rise in serum DHA and EPA after Lovaza administration. Although we did not observe this, we did find an inverse relationship between baseline EPA levels and the increase in serum EPA levels after 1 year.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2012

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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 X25%) 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 þ 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 (Po0.05). Lovaza decreased serum triglycerides and increased high-density lipoprotein (HDL) cholesterol compared with control (Po0.05 for both). Ral reduced serum IGF-1 in a dose-dependent manner (Po0.05) 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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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…3) strengthen the conclusion of a relationship between fatty acid levels and detection of cytologic atypia. Supplementation of long-chain omega-3 fatty acids is a safe and effective method of increasing tissue concentration (46); therefore, we hypothesize that supplementation of long-chain omega-3 fatty acids may correct cytologic abnormalities by balancing the ratio of omega-3 and omega-6 fatty acids in tissue. We explored the effects of long-chain omega-3 fatty acid supplementation on breast tissue in parallel pilot studies of 3.4-g EPAþDHA ethyl esters per day for 6 months in premenopausal and postmenopausal women, with cytomorphology and proliferation as response endpoints.…”

Section: Discussionmentioning

confidence: 99%

Omega-3 and Omega-6 Fatty Acids in Blood and Breast Tissue of High-Risk Women and Association with Atypical Cytomorphology

Hidaka

Harvey

et al. 2015

Cancer Prevention Research

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The ratio of omega-3 to omega-6 fatty acids, especially the longchain eicosapentaenoic acid (EPA) þ docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPAþDHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPAþDHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation. Cancer Prev Res; 8(5); 359-64. Ó2015 AACR.

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“…Past studies of o3 have used food frequency questionnaires, 25 diaries to register major deviations from the usual diet, 26 self-reported compliance, 27 and pill counts [28][29][30] to measure compliance. However, all of them rely on the accuracy of the information that the subject provides and therefore their reliability is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cell Fatty Acid Analysis for Determining Compliance with Omega3 Supplements in Dry Eye Disease Trials

Gadaria-Rathod

Dentone

Peskin

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To evaluate pill counts and red blood cell (RBC) membrane fatty acid profiles as measures of compliance with oral omega3 polyunsaturated fatty acids (o3 PUFAs) and to compare the two techniques. Methods: Sixteen dry eye disease subjects were given oral o3 PUFA or placebo for 3 months. Compliance was measured by pill counts and blood tests at baseline and 3 months. The Wilcoxon signed-rank tests and rank-sum tests were used to compare changes from baseline and the difference between the two groups; Spearman correlation coefficients were used to assess the relationship of pill counts to changes in blood FAs. Results: Pill counts for the o3 (n = 7) and placebo (n = 9) groups showed a mean consumption of 4.39 and 4.76 pills per day, respectively. In the o3 group, the median change from baseline was + 1.46% for eicosapentaenoic acid (EPA) (P = 0.03), + 1.49% for docosahexaenoic acid (DHA) (P = 0.08), and -1.91% for arachidonic acids (AA) (P = 0.02). In the placebo group, median changes in all measured FAs were small and not statistically significant. The difference in change in FA levels between the two groups was significantly greater for EPA (P = 0.01) and AA (P = 0.04). The correlations between pill counts and changes in EPA (r = 0.36, P = 0.43) and DHA (r = 0.17, P = 0.70) were not strong. Conclusions: RBC FA analysis can be used to measure compliance in the active group and also monitor the placebo group for nonstudy o3 intake. Low correlation of pill counts with blood levels suggests that pill counts alone may be inaccurate and should be replaced or supplemented with objective measures.

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ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition

Cited by 82 publications

References 33 publications

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

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

Omega-3 and Omega-6 Fatty Acids in Blood and Breast Tissue of High-Risk Women and Association with Atypical Cytomorphology

Red Blood Cell Fatty Acid Analysis for Determining Compliance with Omega3 Supplements in Dry Eye Disease Trials

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