Long chain omega-3 (n-3) poly unsaturated fatty acids (LCPUFA) have anti-inflammatory effects and are able to counteract the effects of the pro-inflammatory omega-6 (n-6) fatty acids such as arachidonic acid (AA) by substituting for the n-6 fatty acids in triglycerides (TG) and phospholipids (PL). Several pre-clinical, observational, and case control studies suggest that intake or tissue content of n-3 LCPUFA such as eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), relative to intake or tissue content of long chain n-6 fatty acids such as AA may be associated with reduced risk of breast cancer. The goal of this study was to determine the relationships between dietary intake of fatty acids, tissue levels of fatty acids, and breast tissue biomarkers for risk of breast cancer.

Methods: Women (n=74) were recruited from a clinic in which women at increased risk for breast cancer had breast tissue acquired by random periareolar fine needle aspiration (RPFNA). Breast epithelial cells were assessed for cytomorphology and proliferation (Ki-67 immunochemistry). Fatty acid dietary intake was assessed with the National Cancer Institute Diet History Questionnaire. Plasma, erythrocyte, and breast specimens were processed for membrane PL and TG and analyzed for individual fatty acids by gas liquid chromatography.

Results: Total intake of n-3 PUFA was 1.1 ± 0.5 g/d, and the ratio of EPA+DHA:AA was 0.1:1.0 (n=66). Dietary n-3 LCPUFA correlated with n-3 LCPUFA in both plasma and erthyrocyte PL (n=62). Breast epithelial cell number, Masood cytomorphology score, and percent Ki-67 positive cells were higher in RPFNA specimens which exhibited cytologic atypia compared to those which did not (n=74; p<0.001, Mann-Whitney Test). Subjects with atypia consumed less dietary n-3 PUFA (n=66, p=0.020), had lower plasma and erythrocyte PL and plasma TG EPA, DHA, total n-3, and EPA+DHA:AA (n=70; p<0.05). In breast tissue TG, the ratio of n-3:n-6 was also lower in subjects with atypia (n=40; p=0.025).

Conclusions: Overall, women in this high risk cohort consumed very low amounts of n-3 LCPUFAs. Dietary intake of n-3 LCPUFA was related to levels of n-3 LCPUFA in erythrocyte and plasma PL. Given the association of low levels of n-3 fatty acids with cytologic atypia (a known risk factor for breast cancer development), an intervention to increase n-3 fatty acids and n-3:n-6 ratios has merit and clinical trials in high risk women have been initiated.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-03.