The present nested case-control study was designed to investigate whether the association between carotenoid consumption and risk of breast cancer is related to mammographic density. High breast density as measured by mammography has been reported to be a powerful indicator of increased breast cancer risk. The study included 604 breast cancer cases and 626 cancer-free controls in the Nurses' Health Study for whom circulating carotenoid (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) levels had been measured and mammograms obtained prospectively. Using a computer-assisted method to determine mammographic density, circulating carotenoids were not found to be associated with mammographic density. However, mammographic density significantly influenced the association between total circulating carotenoids and risk of breast cancer (P heterogeneity = 0.008). Total circulating carotenoid levels were found to be inversely associated with overall breast cancer risk (P trend = 0.01). Among women in the highest third of mammographic density, total circulating carotenoids were associated with a 50% lower risk of breast cancer (odds ratio = 0.5; 95% confidence interval = 0.3 - 0.8). Similarly, among these women, high levels of circulating alpha-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were found to be associated with a significant 40% to 50% reduction in risk of breast cancer (P trend < 0.05). On the other hand, no such inverse association was observed between circulating carotenoids and breast cancer risk among study participants with low mammographic density. The authors conclude that plasma levels of carotenoids may play a role in reducing risk of breast cancer, especially among women with high breast density.

The present study was designed to investigate how histone deacetylase (HDAC) inhibition affects tamoxifen-induced autophagy in breast cancer cells. Autophagy is a type of cell self-digestion which can stop normal cells from developing into cancer cells and lead to cell death. However, autophagy can also protect breast cancer cells by neutralizing the effectiveness of anticancer drugs. Most patients with estrogen receptor-positive (ER+) breast cancer who experience an initial response to tamoxifen or aromatase inhibitors eventually develop resistance. In fact, many breast tumors are resistant to anti-estrogens from the outset of treatment. One of the known survival strategies of breast cancer cells treated with hormone therapy is the induction of autophagy. During autophagy, cellular components are catabolized in autophagic lysosomes, enabling the removal of damaged organelles and recycling of nutrients during periods of starvation. Treatment with both aromatase inhibitors and tamoxifen has been shown to be associated with upregulating expression of the essential autophagy protein beclin-1. Reduction of autophagy in breast cancer cells increases the cytotoxicity of tamoxifen, suggesting that autophagy in such cells is oncogenic and that autophagy is a potential contributor to tamoxifen resistance. The authors have demonstrated that the cytotoxicity of tamoxifen in breast cancer cells is enhanced by HDAC inhibitors, raising the possibility that HDAC inhibitors achieve synergy with tamoxifen by inhibiting autophagy. In the current study, several HDAC inhibitors were found to cause a synergistic increase in apoptosis and cell death in combination with tamoxifen. Adding an HDAC inhibitor to tamoxifen resulted in enhanced autophagy, in a time- and dose-dependent manner. However, HDAC inhibition promotes transition from autophagic cell preservation to apoptotic cell death. Functional estrogen-mediated signaling was found to be required for such increased autophagy; depletion of ER by siRNA or treatment with fulvestrant did not result in increased autophagy. The authors note that breast cancer cells react with an autophagic survival response as a result of nutrient starvation, tamoxifen treatment, and exposure to DNA damaging agents. The study findings further suggest that HDAC inhibitors act in synergy with tamoxifen to prevent the excess of autophagic lysosomes from sustaining self-preservation, thereby triggering elimination of cells by apoptotic cell death in a fatal switch. The authors conclude that combining tamoxifen with an HDAC inhibitor may represent a new therapeutic approach to overcome hormone therapy resistance.

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] is an isothiocyanate in cruciferous vegetables with a number of potential chemopreventive actions. The current study examined the effects of sulforaphane on the proliferation of human MCF-7 breast cancer cells and on the expression of estrogen receptor α (ERα) protein and mRNA in the cells. Sulforaphane was found to inhibit cell proliferation and ERα protein expression. Lowered ERα expression was also found to be accompanied by decreased progesterone receptor expression. MCF-7 cell mRNA expression was inhibited by sulforaphane at relatively high doses, but not at low sulforaphane concentrations. The authors conclude that sulforaphane can inhibit proliferation of MCF-7 breast cancer cells and down-regulation of hormone receptor expression.

Indole-3-carbinol, a phytochemical derived from cruciferous vegetables such as broccoli and brussels sprouts, is a powerful antiproliferative in human breast cancer cells and can decrease metastatic spread of tumors in experimental animals. The current study demonstrated that indole-3-carbinol significantly decreased the in vitro migration of MDA-MB-231 breast cancer cells, a highly invasive cell line. The data demonstrated that indole-3-carbinol induces stress fibers and peripheral focal adhesions and that this leads to a reduction in motility of human breast cancer cells.

The present study determined how cooking influenced in vitro bile acid binding of various vegetables using a mixture of bile acids secreted in human bile under physiological conditions. Greater bile acid binding potential has been associated with lower risk of heart disease and cancer. The bile acid binding capacity of food and food components has been related to their cholesterol-lowering potential. Lowered recirculation of bile acids results in the use of cholesterol in the body to synthesize bile acid and reduced fat absorption. Secondary bile acids have been related to increased risk of cancer. Incubations were conducted for each treatment simulating gastric and intestinal digestion. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was used as the positive control treatment and cellulose as the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was 13% for the collard greens, mustard greens, and kale; 10% for broccoli; 8% for Brussels sprouts and spinach; 7% for green bell pepper; and 5% for cabbage. These results point to the significantly different (P ≤ .05) health-promoting potential of the vegetables, with collard greens, mustard greens and kale in the top group. Steam cooking was found to significantly improve the in vitro bile acid binding of collard greens, mustard greens, kale, broccoli, green bell pepper, and cabbage compared to the bile acid binding values for these vegetables in raw form. The authors conclude that when consumed regularly after steam cooking, including more of these green and leafy green vegetables would lower the risk of cardiovascular disease and cancer.

The current case-control study was designed to compare the diets of a group of Korean breast cancer patients with a healthy control group. The cases included 97 women with newly confirmed diagnoses of breast cancer at the inpatient or outpatient clinic of Yeouido St. Mary’s Hospital in Seoul, and excluded women with any history of liver diseases, diabetes mellitus, respiratory disorders and cardiovascular diseases. The 97-person control group also excluded women with known malignant, hormonal, gynecological or endocrine diseases. Intake of nutrients in 117 food items were estimated in the breast cancer patients and age-matched healthy controls using a quantitative food frequency questionnaire administered by a trained dietitian. The questionnaire also included general information (age, sex and marital status), age at menarche, and pregnancy history. It was found that the average caloric intake of the breast cancer patients and the healthy controls did not differ significantly. However, the breast cancer patients consumed significantly less fat and antioxidant nutrients such as vitamin A, retinol, beta-carotene, vitamin C and vitamin E than did the controls. Consumption of eggs (p<0.01), legumes (p<0.05), vegetables (p<0.05), seasonings (p<0.001), and oils and fats (p<0.01) was significantly lower in the breast cancer patients. However, the level of energy from fat is relatively low in Korean patients compared to their Western counterparts, and fat consumption may not be an independent risk factor at this level of intake. With respect to particular foods, in addition to eggs, the breast cancer patients consumed a significantly lower quantity of bean curd (tofu), onion, garlic, green pepper, sweet pepper, kale, cucumber, seasoned bean sprouts, sesame leaf, zucchini, radish, mushroom, crown daisy, red pepper paste, bean paste, spicy bean paste, orange juice, grape juice, and tomato juice than the controls. On the other hand, the breast cancer patients consumed significantly greater quantities of cooked rice, noodles, deep fried chicken, satsuma mandarin, Korean melon, kimchi and coffee than the controls. The authors conclude that since the breast cancer patients consumed less soy and vegetables, they had a lower intake than the controls of rich sources of antioxidant nutrients, phytosterols, fiber and non-nutritional components that may reduce the risk of cancer. In addition, the breast cancer patients in this study consumed lower quantities of red pepper paste, bean paste and spicy bean paste, causing their intake of pepper flavonols (which may have a protective effect on breast cancer risk) to be lower than that of the controls.

The current placebo-controlled, parallel-arm pilot study was designed to examine the effects of two naturopathic interventions on sex steroid hormones and metabolic markers. Study participants included 40 healthy premenopausal women who were tested over five menstrual cycles. Two types of intervention were evaluated. Fifteen women were given a combination herbal supplement containing Curcuma longa, Cynara scolymus, Rosmarinus officinalis, Schisandra chinensis, Silybum marinum, and Taraxacum officinalis. Ten women made dietary changes, including consuming three servings of crucifers or dark leafy greens, 30 grams of fiber, and one to two liters of water per day, as well as limiting caffeine and alcohol consumption to one serving per week. Fifteen women served as control (placebo). Early-and late-follicular phase blood samples from cycles one and five were assessed for estrogens (estrone, estrone-sulfate, total estradiol, and free estradiol), androgens (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and free testosterone), sex hormone-binding globulin, and metabolic markers (insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin). Additional blood and urine samples were also collected and analyzed. During the early follicular phase, the herbal supplement was found to decrease the androgens dehydroepiandrosterone (−13.2%; P = 0.02), dehydroepiandrosterone-sulfate (−14.6%; P = 0.07), and androstenedione (−8.6%; P = 0.05), as well as the estrogen estrone-sulfate (−12.0%; P = 0.08) compared with the placebo group. No other trends or statistically significant changes were found. In particular, the dietary changes resulted in no statistically significant changes in sex steroid hormones or metabolic markers. The authors conclude that, in this pilot study, the interventions had no substantial effects on estrogen measures. However, early-follicular phase androgens declined in the women taking the botanical supplement.

The current study was designed to assess the phenolic composition of vegetables commonly consumed by African Americans in the southeastern U.S. using high performance liquid chromatography/mass spectrometry. Vegetables studied included collard greens, mustard greens, sweet potato greens, kale, okra, green onion, rutabagas, butter beans, butter peas, purple hull peas, eggplant, and purslane. The following five main phenolic compounds were identified: caffeic acid, ferulic acid, isorhamnetin, quercetin and kaempferol. No myricetin, luteolin, apigenin, gallic acid, p-coumaric acid, hesperetin, naringenin, or flavanols were detected. Isorhamnetin, quercetin and kaempferol were the major flavonoids detected. Isorhamnetin was found in kale, mustard greens, and purslane, with content ranged from 2.8 to 23.6 mg/100 g fresh edible portion. Quercetin was present in mustard greens, collard greens, kale, sweet potato greens, okra, purple hull peas, and purslane, with content varying from 1.3 to 31.8 mg/100 g. The highest quercetin content was found in kale, whereas the lowest was in purslane. Kaempferol was found in mustard greens, collard greens, kale, sweet potato greens, green onion, and purslane, with content again varying greatly, from 1.1 to 90.5 mg/100 g. Caffeic acid was detected only in sweet potato greens. Ferulic acid was found in mustard greens, collard greens, kale, okra, purple hull peas, and purslane. Although the results indicated that bioactive compounds were probably also present in eggplant, butter beans, butter peas and rutabagas, the compounds were not identified due to lack of reference compound and no flavonoid or phenolic acid was quantified in these samples. The authors conclude that vegetables traditionally consumed among African Americans are good sources of some phenolic compounds useful for the prevention of cardiovascular and other chronic diseases.

The present population-based case-control study was designed to determine whether fruit, vegetable, and antioxidant micronutrient consumption was associated with a reduction in breast cancer incidence. Included were 1,463 breast cancer cases and 1,500 controls. Participants completed a food frequency questionnaire, which enabled assessment of the frequency and amount of 13 fruits and fruit juices and 16 vegetables. Also recorded was any use of multiple or single vitamin supplements. Included in the analysis was menopausal status and the clinical characteristics of the breast cancer cases. After controlling for age and energy intake, it was found that for postmenopausal women, the risk of breast cancer was lower for the highest quintile compared to the lowest quintile of consumption of any vegetables [odds ratios (OR), 0.63; 95% confidence intervals (CI), 0.46–0.86; P for trend (P) < 0.01] and leafy vegetables [OR=0.66; CI, 0.50–0.86; P = 0.03]. Adjusted ORs (95% CIs) were also lower for postmenopausal breast cancer in relation to high intake of carotenoids, α-carotene, ß-carotene, lutein, and, notably, lycopene [OR=0.66; CI, 0.48–0.90; P = 0.03]. Inverse associations for fruits and vegetables were strongest for postmenopausal women with estrogen receptor positive (ER+) tumors (OR=0.65; CI, 0.51–0.82) rather than ER– tumors (OR=0.92; CI, 0.64–1.32), but results were less consistent for micronutrients. No similar associations were observed among premenopausal women. Odds ratios did not appreciably differ by whether the cases were in situ or invasive breast cancer or by whether the cases had begun chemotherapy. The authors conclude that there is an inverse association between fruit and vegetable intake and breast cancer risk among postmenopausal but not premenopausal women and that this association may be stronger for women with ER+ tumors.

Animal studies have shown that intake of the carcinogen benzo[a]pyrene, a polycyclic aromatic hydrocarbon, causes increases in tumor levels, particularly in the upper gastrointestinal tract. However, the role of benzo[a]pyrene in food and cancer in humans is unclear. The authors created a benzo[a]pyrene database of selected foods that could be used in combination with a food frequency questionnaire to estimate benzo[a]pyrene intake. Meat samples were prepared by different cooking techniques in controlled conditions, and by several restaurants and fast-food chains. Other foods were purchased from major national supermarket chains. Benzo[a]pyrene levels were measured for each food. The database was linked to the results from the food frequency questionnaire to estimate the daily benzo[a]pyrene intake through food in 228 subjects in Washington, DC. The highest concentrations of benzo[a]pyrene (up to approximately 4 ng benzo[a]pyrene/g of cooked meat) were found in grilled or barbecued very well done steaks and hamburgers and in grilled or barbecued well done chicken with skin. Benzo[a]pyrene levels were found to be lower in meats that were grilled or barbecued to medium done and in all broiled or pan-fried meat samples independent of doneness level. The benzo[a]pyrene levels in non-meat items generally were low. However, some cereals and greens (e.g. kale, collard greens) had levels of benzo[a]pyrene up to 0.5 ng/g. In the study population, the bread/cereal/grain and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the average daily intake of benzo[a]pyrene.