Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17ß-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.

Efficacy of low fat diet in the treatment of benign breast disease.

BACKGROUND: Previous studies have shown that lipid abnormalities have a role in the pathogenesis of benign breast disease. However, few investigators have tried to reduce dietary fat to treat this disorder. METHODS: Between 1990 and 1993, we conducted a prospective cohort study to find out the efficacy of a low fat diet (less than 15% fat-derived calories) in the treatment of benign breast disease in patients who had been symptomatic for 6 months or more. The study was conducted in two phases. In the first phase 36 patients were alternately assigned to control and treatment groups for 6 months and in the second phase 121 patients (including all those in phase I) were given treatment (median follow up 25 months, range 3 to 39 months). Detailed lipid profiles were studied at the time of presentation and at 4 and 5 months. RESULTS: Phase I results showed that after 6 months none of the patients in the control group had experienced any alteration in their symptoms and signs but in the treatment group 12 out of 17 improved. In phase II improvement in pain (68 out of 97; 70%), nodularity (51 out of 79; 64%) and discharge (15 out of 19; 80%) was seen. There was a significant decline in the mean values of total cholesterol and high-density lipoproteins at the end of 5 months of treatment. CONCLUSION: A low fat diet improves the symptoms as well as the lipid profile in patients with benign breast disease.

A randomized controlled trial of dietary fat reduction: the retention of subjects and characteristics of drop outs.

We have examined the feasibility of carrying out a randomized controlled trial of dietary fat reduction in women at increased risk for breast cancer. The randomization was either to a control group who were taught the principles of balanced nutrition, but were not counselled to change their fat intake, or to an intervention group who were taught to reduce their dietary fat intake to 15% of total calories from a baseline average of 35% of calories. Potentially eligible subjects were women attending a breast diagnostic clinic who had the mammographic pattern of dysplasia. Subjects were recruited by letter from their referring surgeon followed by a telephone call. Subjects interested in participating in the study then entered by one of two phases. In Phase I, the study was explained, informed consent sought and willing subjects randomized to the intervention or control group. Using this procedure 227 subjects were randomized and 48 (21%) dropped out of the study in the 12 months following randomization. (A drop out was defined as a subject who persistently failed to keep appointments and provide nutrient data.) Of these drop outs, 30 (63%) occurred at or soon after randomization. A modified procedure of entry was then adopted in which subjects interested in the study were first taught the procedures involved, including keeping food records and clinic appointments, and were then asked to provide consent and randomized. Two hundred and eighty subjects were enrolled using this modified procedure and 25 (9%) have dropped out in the 12 months following randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy.

21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

Effects of caffeine-free diet on benign breast disease: a randomized trial.

There is considerable interest in the potential effect on benign disease of a diet free of methylxanthines (caffeine, theophylline, and theobromine) found in coffee, tea, colas, and chocolate. We randomly assigned 158 women who presented with a breast concern either to a group encouraged to abstain from methylxanthine-containing foods and beverages or to a group who received no dietary recommendations (controls). At the initial visit each patient's sociomedical history and data on methylxanthine consumption were obtained by interview, and clinically palpable breast findings were graded on a scale of 0 to 4 (no nodularity to confluent hard "dysplasia") for each quadrant of both breasts. On the follow-up visit approximately 4 months later similar information was obtained. Mammograms were taken at both visits for a subset of women in each group. We found a statistically significant reduction in clinically palpable breast findings in the abstaining group as compared with controls, but the absolute change was minor and may be of little clinical significance. Comparison of before-after mammograms offered little support for the methylxanthine hypothesis. There was no relation between clinically palpable breast finding scores at initial examination and caffeine consumption levels reported at that time.