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Many women in industrialized countries are overweight. Excess body fat is associated with excess morbidity and mortality from atherosclerosis and diabetes. In some cases, overweight/obesity also is implicated with increased incidence of breast cancer, but the results of these studies are not consistent. Human breast cancer is usually distinguished as either premenopausal or postmenopausal. In this review, we focus on literature that presents body mass index (BMI, weight/height2) ranges and identifies menstrual status. The majority of the relevant prospective studies support an inverse relationship between BMI and the relative risk (RR) of developing premenopausal breast cancer. In contrast, a positive relationship between BMI and the RR of developing postmenopausal breast cancer is reported in only half of all prospective studies on this topic. Those studies that do not show a positive RR, in general, have used younger postmenopausal women, and their body weights were obtained prior to menopause. Many case-control studies also report an inverse association between BMI and the RR of developing premenopausal breast cancer, and a positive association between BMI and the RR of developing postmenopausal breast cancer. Other studies do not find these associations, but a number of these studies have used small sample sizes and, for the postmenopausal subjects, have represented populations with low obesity and/or breast cancer rates. Other factors that might play a role in breast cancer development, such as body fat distribution, weight at earlier ages, and weight gain, are also addressed, as well as the effect of obesity in breast cancer prognosis. In addition, limited data available for animal studies related to this topic, as well as potential mechanisms by which body fat may play a role in breast cancer development, are discussed. Finally, the need for better animal models in which to perform controlled dietary and/or drug intervention studies to test rigorously the proposed mechanisms by which body fat may contribute to breast cancer development is addressed.