Obesity and Cancer: The Risks, Science, and Potential Management Strategies

Anne McTiernan has provided a comprehensive and balanced review of a complex topic, namely, "Obesity and Cancer: The Risks, Science, and Potential Management Strategies." The impressive weight of assembled evidence from the cited observational studies has been sufficient to influence several cancer organizations, including the American Cancer Society and the American Institute for Cancer Prevention, to issue recommendations regarding nutrition and physical activity in relationship to cancer.[1,2] However, clinical practice is unlikely to undergo substantial change in the absence of prospective trials demonstrating benefit on clinical outcomes.[3] For at least the breast cancer and obesity question, information from phase III randomized, prospective clinical trials evaluating lifestyle intervention influence on clinical outcome are anticipated in the near future. There are currently no full-scale studies evaluating weight loss as related to either breast cancer incidence or recurrence. However, women who are obese are more likely to have higher dietary fat intake and lower physical activity when compared to nonobese women. In addition, in at least some observational reports, all three factors (obesity, higher fat intake, and lower physical activity) have been related to breast cancer outcome.[4-7] There are several randomized clinical trials currently evaluating dietary lifestyle inter- ventions that incorporate fat-intake reduction, and in some cases, other nutrients, to begin to address the potential role of lifestyle change on breast cancer outcomes.[8-11] These trials will directly address the contribution of dietary fat intake to breast cancer outcome; at least two of these studies will report on clinical end points this year. The WINS Study
The Women's Intervention Nutrition Study (WINS) has entered 2,400 women 48 years of age or older with early-stage, resected breast cancer. The women have been randomized to either control or dietary intervention groups, with the latter designed to result in dietary fat-intake reduction.[12] All hormone receptor-positive patients received tamoxifen(Drug information on tamoxifen); protocoldefined chemotherapy is required for receptor-negative patients, while chemotherapy is optional for those with receptor-positive disease. Counseling on weight loss is not an intervention target. Adherence to the intervention has been presented.[9] Clinical outcome results after about 5 years of median follow-up are anticipated for mid-2005. The major study end point, similar to adjuvant chemotherapy or hormonal therapy trials, is relapse-free survival including breast cancer recurrence and contralateral breast cancer development. The Women's Health Initiative Dietary Modification Trial
The dietary modification trial of the Women's Health Initiative is also a randomized, prospective multicenter clinical trial evaluating a lifestyle intervention vs a control condition.[ 11,13] The dietary intervention is a low-fat dietary pattern that is high in fruits, vegetables, and grains, hypothesized to reduce the risk of breast and colorectal cancer, and secondarily coronary heart disease, in otherwise healthy postmenopausal women. Accrual has been completed, with 48,836 postmenopausal women randomized and undergoing follow-up. Intermediate dietary adherence has been described.[14] By study design, outcomes will be evaluated and results presented following 8.5 years of follow-up later in 2005. The results from these two studies, separately evaluating the effect of dietary fat intake on breast cancer recurrence and breast cancer incidence, may provide the first definitive evidence sufficient to move lifestyle intervention strategies into active clinical practice.