Dietary Interventions

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Epidemiologic observations of large international differences in the incidence of breast cancer have provided a basis for formulating hypotheses on a possible relation between diet and the development of cancer. The age-adjusted incidence of breast cancer varies from 22 per 100,000 in Japan to 68 per 100,000 in the Netherlands.116 The ratio of breast cancer mortality between the United States and Japan is 3:1 for premenopausal women and 8:1 for postmenopausal women.117 These important differences may possibly be related to fat intake and total calories in the diet. Clinical data collected from case-control studies have demonstrated a positive correlation between diets high in fat and meat and breast cancer.118-122 Experimental studies have shown that omega-6 polyunsaturated fatty acids (PUFAs) contained in high-fat diets promote both mammary tumorigenesis and cell proliferation in chemically induced mammary tumors, whereas omega-3 PUFAs, contained in fish oil, can inhibit these effects.119120

Heterocyclic amines, a group of mutagenic compounds identified in cooked foods, seem to be related to the increased risk of breast cancer associated with high intake of well-done meat. Recently, a case-control study among 41,836 women demonstrated that women who consumed well-done meats, including hamburger, beef steak, and bacon, had higher adjusted odds ratios for breast cancer (up to 4.62), if they consumed all three different meats well done.121

These data have provided the rationale for diet interventions, consisting of a low-fat diet and fish-oil supplements, that have been found to be able to produce increases in total omega-3 PUFAs in adipose tissue and in the ratio of omega-3/omega-6 PUFAs in patients with breast cancer.120 The Canadian Diet and Breast Cancer Prevention Study Group has conducted a multicenter randomized trial involving women with breast densities detected on mam-mography and showed that after 2 years of a low-fat diet, with less than 15 percent of calories from fat, there was a significant reduction in the number of radiographic abnormalities.122 Adjuvant dietary recommendations of 15 percent of calories from fat for women with post-menopausal breast cancer are currently being evaluated in the Women's Intervention Nutrition Study and in the Women's Healthy Eating and Living Study.123

The role of alcohol consumption and smoking are also being extensively investigated as possible risk factors for breast cancer. While the majority of the studies has documented that high alcohol intake is associated with a significant increased incidence of breast cancer, no definitive pathogenetic role for active or passive smoking has been demonstrated.124125

The use of natural products contained in essential oils and soy-based products, for example, the monoterpenes limonene and perillyl alcohol and the isoflavonoid genistein, all showed preclinical evidence of tumor regression.126-129 The effects of limonene and limonene-related monoterpenes, perillyl alcohol and perillic acid, on cell growth, cell cycle progression, and expression of cyclin D1 has been investigated in T-4D, MCF-7, MDA-MB-231 breast cancer cell lines. The results revealed that limonene-related monoterpenes caused a dose-dependent inhibition of cell proliferation. Of the three monoterpenes tested, perillyl alcohol was the most potent and limonene was the least potent inhibitor of cell growth. Growth inhibition induced by perillyl alcohol and perillic acid was associated with a fall in the proportion of cells in the S phase, accumulation of cells in the G1 phase, and a decrease in cyclin D1 mRNA levels.128 The potential preventive role of genistein, a component of soy, has been evaluated in rats. Pharma-cologic doses of genistein given to immature rats enhance mammary gland differentiation, resulting in a significantly less proliferate gland that is not as suspectible to mammary cancer.129 These components are presently being tested in several clinical chemopreven-tive studies.

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