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

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

Dietary patterns of early childhood and maternal socioeconomic status in a unique prospective sample from a randomized controlled trial of Prenatal DHA Supplementation

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background Dietary habits established in early childhood and maternal socioeconomic status (SES) are important, complex, interrelated factors that influence a child’s growth and development. The aim of this study was to define the major dietary patterns in a cohort of young US children, construct a maternal SES index, and evaluate their associations. Methods The diets of 190 children from a randomized, controlled trial of prenatal supplementation of docosahexaenoic acid (DHA) were recorded at 6-mo intervals from 2-4.5 years by 24-h dietary recall. Hierarchical cluster analysis of age-adjusted, average daily intake of 24 food and beverage groups was used to categorize diet. Unrotated factor analysis generated an SES score from maternal race, ethnicity, age, education, and neighborhood income. Results We identified two major dietary patterns: “Prudent” and “Western.” The 85 (45%) children with a Prudent diet consumed more whole grains, fruit, yogurt and low-fat milk, green and non-starchy vegetables, and nuts and seeds. Conversely, those with a Western diet had greater intake of red meat, discretionary fat and condiments, sweet beverages, refined grains, French fries and potato chips, eggs, starchy vegetables, processed meats, chicken and seafood, and whole-fat milk. Compared to a Western diet, a Prudent diet was associated with one standard deviation higher maternal SES (95% CI: 0.80 to 1.30). Conclusions We found two major dietary patterns of young US children and defined a single, continuous axis of maternal SES that differed strongly between groups. This is an important first step to investigate how child diet, SES, and prenatal DHA supplementation interact to influence health outcomes. Trial registration NCT00266825. Prospectively registered on December 15, 2005 Electronic supplementary material The online version of this article (doi:10.1186/s12887-016-0729-0) contains supplementary material, which is available to authorized users

Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer

Obesity induces chronic inflammation and is an established risk and progression factor for triple-negative breast cancers, including basal-like (BL) and claudin-low (CL) subtypes. We tested the effects of dietary supplementation with ethyl esters of the marine-derived anti-inflammatory omega-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA+DHA; Lovaza®) on growth of murine BL and CL mammary tumors. Female ovariectomized C57BL/6 mice were fed a control diet or a diet-induced obesity (DIO) diet with or without EPA+DHA (0.025%, resulting in blood levels of EPA and DHA comparable to women taking Lovaza 4 g/day) for 6 weeks. All mice were then orthotopically injected with Wnt-1 cells (a BL tumor cell suspension derived from MMTV-Wnt-1 transgenic mouse mammary tumors) or M-Wnt cells (a CL tumor cell line cloned from the Wnt-1 tumor cell suspension). Mice were killed when tumors were 1 cm in diameter. EPA+DHA supplementation did not significantly impact Wnt-1 or M-Wnt mammary tumor growth in normoweight control mice. However, EPA+DHA supplementation in DIO mice reduced growth of Wnt-1 and M-Wnt tumors; reduced leptin:adiponectin ratio and pro-inflammatory eicosanoids in the serum; improved insulin sensitivity; and decreased tumoral expression of cyclooxygenase-2 and phospho-p65. Thus, EPA+DHA supplementation in mouse models of postmenopausal BL and CL breast cancer offsets many of the pro-tumorigenic effects of obesity. These preclinical findings, in combination with results from parallel biomarker studies in women, suggest EPA+DHA supplementation may reduce the burden of BL and CL breast cancer in obese women

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, wit

Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer

Obesity induces chronic inflammation and is an established risk and progression factor for triple-negative breast cancers, including basal-like (BL) and claudin-low (CL) subtypes. We tested the effects of dietary supplementation with ethyl esters of the marine-derived anti-inflammatory omega-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA+DHA; Lovaza®) on growth of murine BL and CL mammary tumors. Female ovariectomized C57BL/6 mice were fed a control diet or a diet-induced obesity (DIO) diet with or without EPA+DHA (0.025%, resulting in blood levels of EPA and DHA comparable to women taking Lovaza 4 g/day) for 6 weeks. All mice were then orthotopically injected with Wnt-1 cells (a BL tumor cell suspension derived from MMTV-Wnt-1 transgenic mouse mammary tumors) or M-Wnt cells (a CL tumor cell line cloned from the Wnt-1 tumor cell suspension). Mice were killed when tumors were 1 cm in diameter. EPA+DHA supplementation did not significantly impact Wnt-1 or M-Wnt mammary tumor growth in normoweight control mice. However, EPA+DHA supplementation in DIO mice reduced growth of Wnt-1 and M-Wnt tumors; reduced leptin:adiponectin ratio and pro-inflammatory eicosanoids in the serum; improved insulin sensitivity; and decreased tumoral expression of cyclooxygenase-2 and phospho-p65. Thus, EPA+DHA supplementation in mouse models of postmenopausal BL and CL breast cancer offsets many of the pro-tumorigenic effects of obesity. These preclinical findings, in combination with results from parallel biomarker studies in women, suggest EPA+DHA supplementation may reduce the burden of BL and CL breast cancer in obese women

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, wit