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

This excellent summary of the association of overweight and obesity with increased incidence and poorer prognosis in a variety of cancers is well worth the reader's attention. Dr. McTiernan presents literature suggesting that overweight is associated with increased incidence and mortality in a variety of types of cancer. In the case of breast cancer, for which there are more data than any other cancer site, the increased risk of mortality appears to be in part related to increased incidence in postmenopausal women, and to a poorer prognosis associated with both overweight and weight gain following diagnosis. Weight Gain and Overweight: Increased Risks in Breast Cancer
Of particular interest is the fact that weight gain and overweight are associated with increases in risk of recurrence and death from breast cancer as large as those of many longer acknowledged prognostic factors such as nodal status, tumor size, and neu/erbB2 overexpression. In addition, these increases in risk are of the same magnitude as the improvements offered by most known systemic therapies including adjuvant hormonal therapy and chemotherapy. Unfortunately, these data are drawn only from observational settings, as no large randomized trials of weight loss or exercise interventions in the adjuvant breast cancer setting have been carried out as yet. The suggested associations of weight gain and overweight with breast cancer incidence and prognosis are perhaps easiest to explain. It is well known that heavier women have higher estrogen levels, which may in turn act as promoters of breast cancer growth. Prostate cancer may be similarly mediated by a hormonal mechanism in which increased estrogen is converted to androgen. The rationale behind the role of overweight in other non-hormonally mediated cancers is less clear and deserves further investigation, but may also be mitogenrelated. It is known, for example, that obesity leads to reduced levels of sex hormone binding globulins, which leads not only to increased levels of free estradiol(Drug information on estradiol) and free testosterone, but to increased levels of insulin, insulin-like growth factors, cortisol, leptin, and cytokines. Obesity may also be associated with reduced immune function and chemotherapy underdosing. Weight Loss and Exercise Interventions
Considering that weight loss and exercise are strongly associated with other health outcome benefits-including reduction in risk of cardiac disease, diabetes, and cerebrovascular accidents- it would seem appropriate that members of the public and patients be counseled to undertake weight loss and exercise in order to reduce their risk of developing cancer or dying from it. More importantly, however, it would seem urgent to undertake some large well-conducted studies of weight loss and/or exercise interventions, particularly in the setting of adjuvant therapy for breast cancer, where overweight and weight gain have some of the strongest data for association with outcome. It seems likely that women in the adjuvant setting would welcome the opportunity to participate in randomized trials of weight loss and/ or exercise interventions, and that definitive results associating these lifestyle interventions causally with an improvement in disease-free and/or overall survival would support efforts to incorporate these interventions into mainstream therapy. Conclusions
In summary, this article should be read by all oncologists-particularly those treating breast cancer. In an era in which obesity and lack of exercise are endemic in North America, large randomized trials exploring the effects of weight loss and exercise on cancer outcomes should be at the top of the priority list for funding agencies. Such interventions, if truly effective in preventing cancer and/or improving prognosis, could fit well with overall health interventions to prevent cardiac disease, diabetes, and cerebrovascular accidents.