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Purpose: Fatigue is a prevalent and burdensome effect of breast cancer. Fatigue has been linked to chronic inflammation, and diets high in antioxidant nutrients have been associated with lesser prevalence and severity of fatigue. Studies are needed, however, to test if antioxidant-rich diets could improve fatigue., Methods: Pilot, randomized, trial conducted between January 2014 and April 2015, to investigate if a 3-month diet rich in fruit, vegetables, whole grains, and omega-3 fatty acid-rich foods, named the fatigue reduction diet (FRD), improved fatigue and sleep compared to an attention control, named the general health curriculum (GHC). 30 stage 0 to III breast cancer survivors, who had completed cancer treatments, were randomized: 15 receiving the FRD and 15 the GHC. Primary outcome was change in fatigue, as measured by the brief fatigue Inventory, from baseline to 3 months analyzed using linear mixed models. Secondary analyses were changes in sleep quality, serum carotenoids, and fatty acids., Results: From baseline to 3-month fatigue improved by 44 ± 39% in FRD compared to 8 ± 34% in GHC (p = 0.01); sleep quality improved by 2.5 ± 3.3 points in FRD, and diminished by 0.9 ± 2.3 in GHC (p = 0.03); serum total carotenoids (p < 0.01), β-cryptoxanthin (p = 0.02), lutein (p = 0.05), zeaxanthin (p = 0.01), lycopene (p = 0.05), omega-3 fatty acids (p < 0.01), and ratio of omega-3:omega-6 fatty acids (p = 0.02) were significantly increased, and percent saturated fatty acids were decreased (p = 0.04) in FRD; γ-tocopherol was significantly increased in GHC (p = 0.03), and there was a significant visit by group difference for α-carotene between the study groups (p = 0.05)., Conclusions: The FRD intervention improved fatigue and sleep in breast cancer survivors compared to the GHC. FRD diet could provide a non-toxic treatment strategy for persistent fatigue.

Long chain n3 fatty acids appear to have beneficial effects in several domains of health relevant to breast cancer survivors. This study evaluated inter-individual differences in serum levels of n3 fatty acids in 40 breast cancer patients who were participating in a pilot study for prevention of weight gain. Significant predictors of baseline n3 fatty acid levels in serum were dietary intakes of n3 fatty acids, BMI, serum levels of carotenoids and TV hours watched/day, accounting for 43% of the variance. Counseling for prevention of weight gain also tended to increase n3 fatty acid blood levels over time during chemotherapy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women., Methods: We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors., Results: There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia., Conclusions: Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

A continuing challenge in weight loss treatment is attaining maintenance of weight loss. The goal of this study was to develop a counseling method that would assist African American breast cancer survivors with weight loss maintenance. In this pilot study, 31 obese breast cancer survivors were recruited. Individualized, dietitian-led counseling by telephone and free Weight Watchers coupons were provided to all participants for 18 months. At the 6-month time point, women were randomized to receive spirituality counseling or not in addition to the standard program. The spirituality counseling was delivered via telephone using an 8-step framework. Subjects were asked to utilize daily meditation or prayer, daily readings, and the recording of thoughts in a journal. Mean weight loss from baseline to 6 months was a modest 2.0% of baseline weight. From 6 to 18 months, there was no further weight change in the spirituality arm and a gain of 0.7% in the dietitian-only arm. Despite little effect on weight loss, it did appear that spirituality counseling positively affected spiritual well-being (FACIT-Sp) scores and dietary quality. The spirituality counseling framework therefore may be further refined and useful for other health promotion studies with African American populations.

Background: A change in diet is known to affect micronutrient levels in blood but to what extent diet can affect micronutrient levels in the breast is not yet well established., Methods: Healthy, premenopausal women with a family history of breast cancer were randomized across four diet arms for 1 year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable, and combination low-fat/high fruit-vegetable diets. Subjects were asked to collect breast nipple aspirate fluid (NAF) at 0, 6, and 12 months, and levels of micronutrients were measured in the fluid., Results: A total of 122 women were enrolled, 97 were retained for 12 months, and sufficient NAF for analysis was available from 59 women at baseline, 49 at 6 months, and 50 at 12 months. Repeated measures mixed-model ANOVA was used to model the data using cholesterol levels and lactation duration as covariates, where appropriate. The high fruit-vegetable intervention, regardless of fat intake, significantly increased total carotenoid levels in NAF. In the low-fat arm, levels of total carotenoids decreased over time relative to control. Levels of total tocopherols and retinol did not change significantly. Levels of 15-F(2t)-isoprostane, a marker of lipid peroxidation, also did not change significantly over time, although there was a decrease observed in the combination arm., Conclusions: These results indicate that total carotenoid levels in NAF can be significantly increased in the breast NAF with a high fruit-vegetable diet. A low-fat diet that was achieved with little increase in fruit and vegetable intake, however, decreased NAF carotenoid levels.

Leptin is an adipocyte-derived hormone involved in regulation of satiety, and it also appears to have a role in breast cancer risk. Leptin therefore might be a useful indicator of the potential preventive effects of weight loss in breast cancer survivors. In this study we examined whether the change in leptin levels could be predicted by weight loss in obese breast cancer survivors. The subjects in this study were participating in a randomized trial of an individualized approach towards weight loss in Detroit, MI. Breast cancer survivors (body mass index of 30-44 kg/m(2)) were enrolled and fasting blood samples were obtained for leptin analysis over 1 year of study. Leptin levels were available from at least two time points for 36 women, and weight change ranged from a gain of 11% to a loss of 25% of baseline weight. Using a repeated-measures regression model, both baseline leptin level and concurrent percent body fat were found to synergistically predict leptin levels. Thus, for women with the same body fat, those with higher baseline leptin levels are predicted to exhibit smaller decreases in leptin with weight loss. Similar results were obtained for body weight and body weight change, but the associations with body fat were stronger. Breast cancer survivors with initially higher leptin levels may differ with regard to regulation of change in leptin during weight loss resulting in relatively smaller changes in leptin with equivalent amounts of weight loss.

Purpose/objectives: To investigate whether quality of life (QOL) assessed before weight loss intervention predicts weight loss and, in turn, what the effect of weight loss is on QOL measures after 12 months in early-stage breast cancer survivors., Design: A clinical trial of a weight loss intervention in breast cancer survivors., Setting: Community-wide recruitment in Detroit, MI., Sample: 39 breast cancer survivors (body mass index = 30-44 kg/m2), within three years of initial diagnosis and at least three months after chemotherapy or radiation therapy., Methods: Participants were randomized to one of three weight loss methods or a control group. The Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL questionnaire was administered at baseline and after the intervention., Main Research Variables: Six subscales of the FACT-An and weight change., Findings: Modest but statistically significant associations were found for the physical and functional subscales of the FACT-An with weight loss for 39 subjects who completed 12 months of the study. Those reporting relatively impaired physical or functional QOL at baseline lost more weight, which accounted for 8%-9% of the weight loss variance beyond that resulting from the diet arm assignment. At 12 months, greater weight loss was associated with significant improvements in overall FACT-An score and in the physical, functional, fatigue, and anemia subscales (p < 0.05)., Conclusions: Relatively low physical function at baseline was not a barrier to weight loss; indeed, it may have been a motivating factor in adherence to the weight loss intervention. Weight loss was associated with improvement in several QOL subscale measures in breast cancer survivors, but the emotional and social subscales were not affected., Implications for Nursing: Counseling for weight loss that includes recommendations for exercise should not be withheld for patients with relatively low physical functioning.

Objectives: Higher plasma micronutrient levels have been associated with decreased cancer risks. The objective of this study was to determine the relative effects of reduced fat and/or increased fruit-vegetable (FV) intakes on plasma micronutrient levels., Methods: Healthy, premenopausal women with a family history of breast cancer (n = 122) were randomized across four diet arms for one year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable and combination low-fat/high FV diets. Levels of plasma micronutrients were measured in plasma at 0, 3, 6 and 12 months., Results: The high FV intervention, regardless of fat intake, significantly increased alpha-carotene, beta-carotene and vitamin C levels in plasma. Only the combination high FV, low-fat intervention significantly increased plasma beta-cryptoxanthin and zeaxanthin levels over time. Although alpha-tocopherol was not affected, a potential concern is that the low-fat intervention resulted in significantly decreased both gamma-tocopherol dietary intakes and plasma levels, regardless of whether or not FV intakes were concomitantly increased., Conclusions: Unlike alpha-tocopherol, gamma-tocopherol plasma levels were decreased by a low fat diet, perhaps because gamma-tocopherol is not generally added to foods nor widely used in vitamin E supplements. The decreased dietary intakes and plasma levels of gamma-tocopherol with a low-fat diet may have implications for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct.

The presence of epithelial cells in breast nipple aspirate fluid (NAF), irrespective of abnormality, has been associated with increased risk of breast cancer in previous studies. We sought to investigate whether the presence of epithelial cells in NAF is associated with nutritional parameters among 71 healthy premenopausal women who participated in the Nutrition and Breast Health Study and provided any samples of NAF during the study. Total of 142 samples which were obtained over a 1-year period of intervention with low-fat and/or high vegetable-fruit diets were available for cytological evaluation. The odds ratios (ORs) and 95% confidence intervals (CIs) for the detection of epithelial cells in NAF were estimated by fitting generalized estimating equations models by quartile level of nutritional parameters. The probability of yielding epithelial cell-positive NAF progressively increased with increasing total fat intake (p=0.001). The OR for the highest quartile level of fat intake, compared with lowest, was 7.22 (95% CI 1.14-45.82). On the other hand, there were a marginally significant inverse association with total fiber intake as well as an weak inverse association with the number of servings of fruit and vegetables. Furthermore, the probability of detecting epithelial cells in NAF decreased with increasing plasma levels of lutein and alpha-carotene (p-values for linear trend; 0.001 and 0.049, respectively). The ORs for the highest versus lowest quartile levels are 0.17 (95% CI 0.04-0.65) and 0.19 (95% CI 0.04-0.91), respectively. These results are generally in support of roles of nutritional factors in breast cancer and thus further studies are warranted.

Non-steroidal anti-inflammatory drugs (NSAIDs) are thought to reduce cancer risk by inhibiting cyclo-oxygenases, resulting in deceased formation of inflammatory mediators and oxidative stress. We examined whether the level of one oxidative stress marker, 15-F(2t)-isoprostane, was affected by NSAID use in plasma and breast nipple aspirate fluids (NAF) of pre-menopausal women who were participating in a dietary intervention trial (n=121). Baseline levels of 15-F(2t)-isoprostane were lower in NSAID users than non-users in both NAF and plasma, although the differences did not persist after intervention. Over the duration of the study, information on NSAID use was collected five times, and average 15-F(2t)-isoprostane levels in both NAF and plasma exhibited a statistically significant trend for decreases with increased frequency of NSAID use. These results indicate that NSAID use can result in lower levels of 15-F(2t)-isoprostane, which may have implications for the effects of NSAID use on breast cancer risk.

This study examined whether subjects who participated in a 12-mo intervention would maintain their diets 1 yr after the study ended and whether the diets of household members were affected. Premenopausal women, who had at least one first-degree relative with breast cancer (n = 122), were randomized to one of four diets: control, low fat (15% of energy), high fruit and vegetable (FV, nine servings per day), and combination low fat, high FV. Study subjects and one household member were asked to complete the Block '95 food-frequency questionnaire (FFQ) at baseline, 1 yr, and 2 yr. Study subjects also completed 24-h recalls and 4-day food records at baseline and Year 1. Fat and FV intakes by all three assessment methods compared reasonably well except that fat intakes by FFQ were somewhat higher. FV intakes by FFQ in the high-FV and combination arms increased significantly from 4 servings per day to about 10 servings per day at Year 1 and 7 servings per day at Year 2. FV intakes increased much more modestly in the low-fat and control arms. Fat intakes in the low-fat and combination arms were lower at Year 1 than Year 2, but mean Year 2 fat intakes of 26-28% were still significantly lower than those at baseline. In household members, the only significant change was a small decrease in energy from fat at Year 1 in the household members of subjects who were in the combination arm. These results indicate that study subjects were making large dietary changes independently of their household members and that fat and FV intakes in study subjects 1 yr after intervention stopped were still substantially different from intakes at baseline.

Objective: To compare the efficacy of different weight loss regimens on body weight loss and metabolic improvement in breast cancer survivors., Research Methods and Procedures: Forty-eight obese breast cancer survivors were randomly divided into four groups and were followed for 1 year: 1) the Control group (subjects did not receive specific nutrition counseling); 2) the Weight Watchers group (subjects were given free coupons to attend weekly Weight Watchers meetings); 3) the Individualized group (a registered dietitian provided one-on-one nutritional counseling); and 4) the Comprehensive group (subjects received individualized dietary counseling and free coupons for the weekly Weight Watchers meetings). At baseline and 3-, 6-, and 12-month data collection visits, a fasting blood sample was obtained for assays. A three-day dietary record was kept during the week before these visits and dietary intake was analyzed., Results: Subjects in the three intervention groups lost weight (Control: 1.1 +/- 1.7 kg; Weight Watchers: -2.7 +/- 2.1 kg; Individualized: -8.0 +/- 1.9 kg; Comprehensive: -9.5 +/- 2.7 kg) and percentage body fat, but only the Individualized and Comprehensive groups had significant losses. Subjects in the Comprehensive group showed the most improvement in cholesterol levels and had reductions in blood leptin levels., Discussion: Because insulin resistance and high blood leptin levels are associated with breast cancer, losing weight to improve these parameters may reduce the risk of recurrence. Only subjects in the Comprehensive group showed significant reductions in body weight and fat, energy intake, and leptin levels. For breast cancer survivors, different weight loss strategies should be considered to assist them in losing weight.

Dietary patterns that involve both a decrease in fat and an increase in fruit and vegetable (FV) intake may decrease cancer risks. In this study, a total of 122 premenopausal women with a family history of breast cancer were randomized into one of four diets for 12 mo: nonintervention, low-fat (15% of energy from fat), high-FV(9 servings/d), and combination low-fat/high-FV Fasting blood samples were obtained at baseline and after 3, 6, and 12 mo. Levels of 8-isoprostane-F2a in plasma were deter-mined by immunoassay kits. Statistical analyses indicated that levels of 8-isoprostane-F2a decreased significantly with time in the low-fat arm, which is the only intervention that resulted in weight loss; there were no significant changes in the other three diet arms. It is unlikely that this is due to changes in levels of blood lipids because there was little change overtime in plasma total cholesterol, high-density lipoprotein,low-density lipoprotein (LDL), or triglyceride levels in any diet arm, although mean LDL did decrease slightly in women who reduced fat intake after adjustment for change in body mass index (BMI). Levels of baseline 8-isoprostane-F2a were significantly higher in obese women than in overweight or normal weight women, and change in BMI was significantly correlated with change in 8-isoprostane-F2a levels. These results indicate that low-fat diets or high-FV diets are unlikely to affect plasma levels of 8-isoprostane-F2a in healthy,premenopausal women who do not lose weight during dietary change.

Objective: Obese breast cancer survivors are a unique population for weight loss counseling because both obesity and a diagnosis of breast cancer can increase the risk of depression. In this pilot study, weight loss maintenance was examined in obese breast cancer survivors with relationship to psychiatric diagnosis., Research Methods and Procedures: Forty-eight subjects were enrolled. The intervention, which used individualized counseling for diet and exercise, lasted 24 months. After a 6-month period of no contact with study subjects, a follow-up body weight was obtained at 30 months., Results: The nine subjects who dropped out of the study before 12 months all failed to complete a structured psychiatric interview. Of the remaining 39 subjects, 9 had major depressive disorder, and 10 had a definable psychiatric disorder of lesser severity such as adjustment disorder. Subjects with any type of psychiatric diagnosis displayed significantly less weight loss at the 12-month time-point than those with no diagnosis (6.3% vs. 12.6% loss of baseline weight, respectively). At the 30-month follow-up visit, subjects with any psychiatric disorder had a mean weight loss of 1.2% of baseline weight compared with 7.8% weight loss in subjects with no diagnosis., Discussion: These results suggest that the presence of psychiatric disorders can interfere with weight loss. Therefore, recognition and treatment of psychiatric disorders may be important in attempts at weight reduction, and this will be especially important in populations such as cancer survivors, who seem to have higher rates of depression and other disorders than the general population.

An high-performance liquid chromatography method with electrochemical detection was developed to quantify both 2,6-cyclolycopene-1,5-diol and lycopene in plasma and breast nipple aspirate fluids (NAF). As an example of the utility of this assay, levels in plasma and NAF of 11 women were examined and compared with levels of 8-isoprostane, a commonly used marker of lipid oxidation. Levels of 2,6-cyclolycopene-1,5-diol and 8-isoprostane were higher in NAF than in plasma, but levels of lycopene were lower in NAF than in plasma. Levels of 2,6-cyclolycopene-1,5-diol in plasma and in NAF were significantly correlated with both lycopene and 8-isoprostane levels. This is consistent with the dependence of 2,6-cyclolycopene-1,5-diol levels on both dietary intakes of lycopene and oxidative stress levels. For the correlations between NAF and plasma, lycopene levels were significantly correlated, whereas 2,6-cyclolycopene-1,5-diol levels were not, indicating that levels of 2,6-cyclolycopene-1,5-diol in NAF are difficult to predict from plasma levels. The high levels of 2,6-cyclolycopene-1,5-diol and 8-isoprostane in NAF are consistent with high levels of oxidative stress in the breast.

Objective: The objective was to develop effective weight-loss methods for women who have had breast cancer, because obesity may result in an adverse prognosis., Research Methods and Procedures: This randomized pilot study tested an individualized approach toward weight loss in obese women who have had a diagnosis of breast cancer. An individualized approach was applied either alone or combined with the commercial Weight Watchers program. Forty-eight women (body mass index of 30 to 44 kg/m(2)) were enrolled., Results: Weight change after 12 months of intervention was as follows (mean +/- SD): 0.85 +/- 6.0 kg in the control group, -2.6 +/- 5.9 kg in the Weight Watchers group, -8.0 +/- 5.5 kg in the individualized group, and -9.4 +/- 8.6 kg in the comprehensive group that used both individualized counseling and Weight Watchers. Weight loss relative to control was statistically significant in the comprehensive group 3, 6, and 12 months after randomization, whereas weight loss in the individualized group was significant only at 12 months. Weight loss of 10% or more of initial body weight was observed in 6 of 10 women in the comprehensive group at 12 months. In the comprehensive and Weight Watchers-only groups, weight loss was significantly related to frequency of attendance at Weight Watchers meetings, and attendance was more frequent in the comprehensive group., Discussion: These data indicate that the most weight loss was achieved when the counseling approach combined both Weight Watchers and individualized contacts. This was effective even though most of the individualized contacts were by telephone.

Background: Dietary intervention research with free-living subjects relies on the ability of study participants to meet their dietary goals within the study timeframe. Little is known about underlying factors affecting compliance., Method: Here, we examined whether motivation to enroll in a trial of low-fat and/or energy-reduced diets influenced the ability of healthy women to reach their dietary goals quickly., Results: Of the women who had energy-reduction goals (n=43), the 18 with an altruistic reason for participation had a much higher energy reduction success rate at 4 weeks (83%) than the 25 who gave self-rewarding reasons (48%)., Conclusions: Education, body weight, family history of cancer and previous diet experience did not appreciably affect dietary outcomes. This observation suggests that the societal importance of the research should be stressed in strategies that seek to affect rapid reduction of energy intake in clinical trials.

Systemic oxidative stress is thought to contribute to risk of various cancers, including breast cancer. DNA repair ability also has been associated with breast cancer risk. In this work, we examined levels of oxidative DNA damage as an indication of breast cancer risk in women because oxidative DNA damage levels should reflect the net balance of oxidative stress and DNA repair ability. Levels of 5-hydroxymethyl-2'-deoxyuridine, one form of oxidative DNA damage, were measured in DNA from blood of women scheduled for breast biopsy. The blood samples analyzed included women whose biopsy results indicated invasive breast cancer, high-risk lesions (atypical hyperplasia or carcinoma in situ), or benign lesions. Mean levels of 5-hydroxymethyl-2'-deoxyuridine were significantly higher in blood of women who had high risk or invasive breast lesions versus women with benign lesions. If atypical hyperplasia or carcinoma in situ are precursor lesions for breast cancer, then these results suggest that oxidative DNA damage may be involved in the cancer process before invasive cancer develops.

Oxidative DNA damage (ODD) can result from numerous endogenous metabolic processes as well as from exposure to environmental and dietary oxidants. One important type of ODD that may have a role in carcinogenesis is the formation of hydroxylated DNA bases. Our major purpose was to determine the potential for subject accrual for a multisite case-control study of ODD and breast cancer risk within a large urban university medical center. We examined the levels of a hydroxylated thymine residue, 5-hydroxymethyl-2'-deoxyuridine in DNA obtained from the peripheral blood of 26 women with breast cancer and an age-matched group of 29 control women without breast cancer. The isolated DNA was analyzed for levels of 5-hydroxymethyl-2'-deoxyuridine by gas chromatography with mass spectral detection. Our recruitment methods resulted in a relatively high yield of eligible cases (72%) and a lower yield of controls (46%). We evaluated the dose-response relationship of ODD level to breast cancer risk, using quartiles of ODD. The covariate-adjusted odds ratio of breast cancer exceeded 2.0 for women in the highest quartile of ODD (compared with the lowest quartile), although this result was not statistically significant. ODD levels were significantly more variable among African-American controls (SD = 224.1) than among white controls (SD = 57.5), p < 0.001. Overall, these results suggest a possible slight increase in breast cancer risk among women in the highest ODD quartile, after adjusting for race, menopausal status, and family history of breast cancer.

Dietary fat and energy intake have been implicated in breast cancer etiology. To examine the relative importance of these dietary factors on markers of cancer risk in women, we designed an intervention trial to selectively decrease fat and/or energy intake in free-living, premenopausal women who were somewhat overweight. The study used a 2 x 2 factorial design to evaluate the independent and interactive effects of dietary fat and energy. The diets were nonintervention, low fat (15% of energy from fat, maintenance of energy intake), low energy (25% energy reduction), and combination low fat and low energy. We utilized an individualized counseling approach with self-selection of foods. Women on the low-fat and combination diets were asked to meet given daily goals for fat grams and food group exchanges, while women on the low-energy diet used only food group exchanges. Of the 113 premenopausal women randomized who were eligible for analysis, 43% were African-American. A total of 88 women completed the 12-week program, and adherence to the dietary goals was similar in both racial groups. Women on the low-fat diet were able to reduce dietary fat intake to 19% of energy by 4 weeks and to 17% by 12 weeks with a slight decrease in energy intake. Women on the low-energy diet met their energy reduction goals by four weeks while maintaining percentage of energy from fat. Women on the combination diet largely met their goals by four weeks as well. These data indicate that it is possible to selectively manipulate dietary fat and energy intake in women over a short period of time, which makes clinical studies on the relative effects of these two dietary variables on cancer risk biomarkers readily feasible.

Objective: We examined the relationship between intakes of specific foods--namely, meats, vegetables, and fruits--with levels of oxidative DNA damage in women consuming their own usual diet or a diet low in fat., Design: Blood was obtained from women who had been assigned randomly to a low-fat or nonintervention diet for 3 to 24 months. Levels of 5-hydroxymethyluracil, a type of oxidative DNA damage, were determined. Diet data were obtained from 3-day food records., Subjects/setting: The 21 women were participating in an outpatient clinic. All the women were healthy but had a first-degree relative with breast cancer., Intervention: The intervention was a self-selected diet with a goal of 15% of energy from fat., Main Outcome Measures: Existing data on oxidative DNA damage levels were evaluated for possible relationships to foods eaten. Intakes of raw and cooked vegetables were examined separately. Meat intake was examined by type of meat (pork, beef, fish, chicken) and by cooking temperature., Statistical Analyses: Initial univariate analyses relied on Spearman rank correlations of each food item with DNA damage. Further analyses of the data were performed with univariate and multivariate weighted least squares regression models., Results: The model that best explained DNA damage levels was a bivariate regression model that included the intake of cooked vegetables and the sum of beef and pork intake. This model accounted for 85% of the variation in DNA damage levels among women. Preliminary results are suggestive of a positive association of DNA damage with beef and pork intake and a negative association with cooked vegetable intake., Application: These observations, if confirmed in larger studies, suggest specific dietary changes to reduce oxidative DNA damage levels and possibly cancer risk.

The growth inhibitory properties of alpha-tocopheryl hemisuccinate (vitamin E succinate) and related compounds were examined in MCF-7 human breast tumor cells and MCF-10A normal-like human breast cells since they have been suggested to be an effective antitumor compound. The data showed that both alpha-tocopherol hemisuccinate and a structurally-similar compound, cholesteryl hemisuccinate, inhibited the growth of MCF-7 and MCF-10A cells, while alpha-tocopherol, cholesterol, cholesteryl sulfate and Tris succinate had little effect on cell growth. The ether analogs of the succinate esters, alpha-tocopheryloxybutyric acid and cholesteryloxybutyric acid, also inhibited growth of MCF-7 and MCF-10A cells, indicating that hydrolysis of the succinate esters by esterases is not required for the antiproliferative effects. The antiproliferative effects of these succinate esters and ethers may be related to their physiochemical properties that allow incorporation into cell membranes.

Background: Oxidative DNA damage can result from numerous endogenous metabolic processes as well as from exposure to environmental and dietary oxidants. One important type of oxidative DNA damage is the formation of hydroxylated DNA bases. This type of DNA damage may have a role in carcinogenesis., Methods: We examined the levels of a hydroxylated thymine residue, 5-hydroxy-methyl-2'-deoxyuridine, in DNA obtained from the peripheral blood of breast cancer patients and control women. The isolated DNA was analyzed for levels of 5-hydroxymethyl-2'-deoxyuridine by gas chromatography with mass spectral detection., Results: The levels of this modified base were significantly higher in 25 breast cancer patients compared with 38 controls, with levels of 0.112 +/- 0.046 in the cancer patients versus 0.083 - 0.025 in the controls, given as pg 5-hydroxymethyl-2'-deoxyuridine/ng thymidine, mean +/- standard deviation (P = 0.019). After controlling for various covariates, the adjusted mean levels of oxidative DNA damage were still significantly higher in women with breast cancer relative to controls., Conclusions: These results indicate that the levels of 5-hydroxymethyl-2'-deoxyuridine in DNA from peripheral nucleated blood may be potentially useful as a marker of breast cancer.

DNA damage induced by oxidants includes formation of DNA strand breaks as well as oxidative damage to DNA bases. We quantified both forms of DNA damage concurrently in two model human breast epithelial cell lines treated with hydrogen peroxide to compare the dose-dependent induction of each form of DNA damage with growth inhibition. Antioxidant defenses also were quantified. MCF-7 breast cancer cells had relatively higher levels of non-protein thiols, oxidized glutathione (GSSG) reductase, catalase, and superoxide dismutase than did the MCF-10A line of immortalized, but not transformed, human breast epithelial cells. The levels of antioxidant defenses were not predictive of endogenous oxidative DNA damage levels nor of toxicity and DNA damage induced by hydrogen peroxide. The endogenous levels of 5-hydroxymethyl-2'-deoxyuridine were higher in MCF-7 than MCF-10A cells. The cells were treated with 10-200 microM hydrogen peroxide for 15 min at 37 degrees C in complete media. Low concentrations of hydrogen peroxide were growth stimulatory to both cell lines. At higher concentrations, growth inhibition by hydrogen peroxide was greater in MCF-7 than in MCF-10A cells. Accordingly, induction of both single-strand DNA breaks and 5-hydroxymethyl-2'-deoxyuridine in DNA was greater in MCF-7 than MCF-10A cells. In both cell lines, the dose-dependent induction of single-strand breaks paralleled growth inhibition more closely than did formation of 5-hydroxymethyl-2'-deoxyuridine.