Abstract
Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration.
Highlights
Prevention is the best approach to reduce breast cancer morbidity and mortality
Baseline variables were similar between women who completed the trial and those that did not, except for body mass index (BMI) which was greater in the latter group
The log absolute breast density was used for this dataset for better fit of linear model, similar results were obtained by modeling absolute density directly. These analyses suggest that DHA and absolute breast density are negatively associated in subjects with BMI > 29 but not on subjects with BMI 29
Summary
Tamoxifen and raloxifene, have been shown to be effective chemopreventive agents [1, 2], they are poorly accepted even by women at high risk primarily because of concerns of side effects such as thromboembolic events which are felt to outweigh the benefit of breast cancer risk reduction [3, 4] Both agents are ineffective against estrogen receptor–negative. In addition to the estrogen receptor, contribute to breast cancer development, we hypothesize that prevention can be improved by combining estrogen receptor antagonists with compounds having a complementary mechanism of action. Because such compounds are to be used in healthy women, they have to be safe without significant side effects. It may be necessary to target www.aacrjournals.org specific populations, such as overweight and obese women, to demonstrate the protective effect of n-3FA against breast cancer
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