The scope of nutrition intervention trials with cancer-related endpoints.

The National Cancer Institute currently is supporting three full-scale dietary modification trials with cancer-related endpoints. These studies are the dietary component of the Women's Health Initiative, designed to determine whether a low-fat diet will reduce the incidence of breast and colorectal cancer and/or coronary heart disease; the Women's Intervention Nutrition Study, designed to test whether a dietary fat reduction program will decrease breast cancer recurrence and increase patient survival; and the Polyp Prevention Trial, designed to determine whether a low-fat, high-fiber diet will reduce the recurrence of adenomatous polyps. Design issues associated with these full-scale dietary modification outcome trials have been addressed successfully in a series of feasibility studies. The ability to achieve a sustained reduction of 50% in dietary fat intake with maintenance of nutritional adequacy has been demonstrated in randomized trials of postmenopausal populations with resected breast cancer and in populations at increased risk for breast cancer. In these studies comparing dietary fat reduction programs with control lifestyles, a series of associated biologic changes, consistent with the self-reported dietary alterations, have been observed. These changes include body weight reduction, serum and/or plasma estradiol concentration reduction, fasting plasma cholesterol concentration reduction, and alteration in free fatty acid levels. Such results provide a substantial basis for reliably estimating the level of adherence that can be anticipated in trials of dietary change, a prerequisite for appropriate calculation of the sample size needed for multicenter, full-scale outcome studies. As a result, the efficacy of a series of dietary alterations (including fat reduction, fiber addition, and/or increased fruit and vegetable intake) on cancer-related endpoints with potential major public health significance (breast cancer recurrence, breast cancer development, and colonic polyp recurrence) now are being addressed definitively in prospective clinical trials.