DIETARY INTERVENTION--WOMEN HIGH RISK FOR BREAST CANCER

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Description: (Applicant s Description) Dietary fat intake and consumption of fruits and vegetables have been suggested to influence breast cancer risk in women. Testing this hypothesis, however, requires quantitative markers of breast cancer risk that will allow assessment of the effect in a timely manner. To evaluate the beneficial effect of reducing and/or increasing the intake of fruits and vegetables on cancer risk in the proposed clinical trial, the applicant plans to measure the levels of oxidative DNA damage and cholesterol oxides. These intermediate biomarkers are indicative of oxidative stress levels, and oxidative stress has been associated with breast cancer risk. Eligible women who have first degree relatives with breast cancer will be recruited from a high-risk clinic. The women who enter the trial will be randomized onto one of four diets: 1) control, 2) low-fat (15 percent of caloric intake without altering intake of fruits and vegetables), 3) high fruit/vegetable (8 servings/day without altering fat intake), and 4) a low-fat diet that is also high in fruits and vegetables. We plan to retain 30 women/diet arm. The 12-month intervention will involve individualized dietary counseling that meets the needs and abilities of each woman. Blood samples, breast fluids (obtained by expression from the nipple) and complete dietary analyses of four-day food records will be obtained at study entry and at regular intervals during the 12 month program. The levels of 5-hydroxymethyl-2'-deoxyuridine, an oxidized thymidine residue, will be assessed in DNA from blood by gas chromatography-mass spectrometry (GC-MS). The levels of cholesterol oxide in serum and breast fluids will be assessed by GC. The morphology of cells in the breast fluids will be assessed by image analysis since morphological changes are expected to be related to levels of oxidative stress. The levels of micronutrients (carotenoids and tocopherols) in serum and breast fluids also will be determined and used as a monitor of fruit and vegetable intake. In addition, micronutrient levels may well influence the other biomarkers. This research on the biological effects of diet in women at high risk for breast cancer is responsive to the "Healthy People 2000" objective of cancer prevention. The use of biomarkers will allow to evaluate the cancer-protective effects of dietary modulation over a relatively short period of time.