How Diet Influences Breast Cancer Risk: Analysis of Tissue Fat, Nutrients, and a Dietary Pattern among High-Risk Women

Abstract

Background: An estimated one in eight women will develop breast cancer. Heredity, time, lifestyle, and chance determine whether and when someone develops the disease. Importantly, behavior explains the majority of the variation in breast cancer risk. Understanding how diet influences breast cancer risk empowers women with accurate information to make healthy decisions. Unfortunately, among all food, beverage, and supplement choices, there is only consensus that drinking more alcohol increases risk. Methods: Seventy women (36 premenopausal and 34 postmenopausal) from the Breast Cancer Prevention Center, a research clinic for those with high-risk, had their benign breast tissue analyzed for evidence of cytologic atypia, which is a biomarker for short-term risk of breast cancer development. The fatty acid composition of several lipid compartments of their blood and breast tissue was analyzed by gas chromatography. Their nutrient and food consumption was estimated using the National Cancer Institute's food frequency questionnaire. The dietary differences between women with atypia and those without evidence of atypia were assessed by comparing (1) tissue fatty acid content by the Mann-Whitney U test, (2) nutrient and food intake by logistic regression after accounting for energy intake, and (3) dietary patterns derived from principal components analysis by logistic regression. Results: Participants consumed ~10 times more n-6 polyunsaturated (PUFA) than n-3 PUFA. Compared to women without atypia, those with atypia had significantly lower n-3 PUFA in their red blood cells and circulating phospholipids, as well as lower total n-3:n-6 PUFA ratios in lipid compartments reflecting recent and long-term intake (all P<0.05). Among premenopausal women, greater consumption of niacin, pyridoxine, folate, vitamin B12, vitamin D, &#945;- tocopherol, selenium, n-3 PUFA, "other vegetables," fish, and soy predicted a lower likelihood of atypia, while higher glycemic load and intake of added sugar, and trans fat were associated with evidence of atypia (all P<0.05). Higher intake of &#948;-tocopherol and "other fruit" were associated with atypia among postmenopausal women (P<0.05). The protective associations of n-3 PUFA and soy intake were only detected for premenopausal participants (both interactions: P=0.001). A Modern-Traditional dietary pattern was identified, with positive scores indicating a more Traditional diet of vegetables, fish, and poultry, and negative scores reflecting a more Modern diet of grains, added sugar, trans fat, and dairy. A more Traditional dietary pattern was associated with (a) higher n-3 PUFA in blood, (b) lower n-6 PUFA in blood and breast tissue, and (c) lower levels of industrially-produced trans fatty acids in blood and adipose (all P<0.05). Each standard deviation increase in Modern-Traditional dietary pattern score was associated with 50% lower odds of atypia (95% CI: 0.26 to 0.88), with a stronger effect among younger participants (interaction for age: P=0.05). Conclusions: Inadequate intake of n-3 PUFA relative to n-6 PUFA may increase the risk of developing breast cancer. Dietary intake of nutrients and foods were more strongly associated with atypia status among premenopausal compared to postmenopausal participants, particularly for n-3 PUFA and soy. A dietary pattern validated by tissue fat content was associated with short-term breast cancer risk among younger women. Taken together a diet with a higher density of nutrients from fish, poultry, and vegetables may protect against breast tumor formation, especially for younger women.