Abstract CN05-03: Energy balance in cancer patients: Are we ready to intervene?

Abstract

Abstract There is growing evidence that aspects of energy balance, including overweight/obesity and physical inactivity are associated with poor outcomes in some cancers, notably breast and colorectal. In breast cancer, evidence is strongest for overweight/obesity; recent evidence suggests physical activity may have important independent associations with outcomes. In colorectal cancer, evidence is strongest for physical activity. Clinical mechanisms that have been postulated for these associations include presentation of cancer at a more advanced stage or receipt of less than optimal therapy in overweight or obese individuals. Potential biologic mechanisms have included sex hormones, insulin and related IGFs, adipocytokines and inflammatory markers. In breast cancer there is growing evidence that insulin (and associated insulin resistance) may play a key role in mediating these prognostic associations - high insulin levels have been associated with increased risk of breast cancer recurrence or death. Breast cancer cells commonly overexpress insulin receptors (frequently a fetal form of the receptor that may hybridize with the IGF-1 receptor) that are not downregulated by circulating insulin; as a result, cancer cell growth may be stimulated by high circulating insulin levels. Observational clinical studies linking energy balance to prognosis of breast and colorectal cancer will be reviewed, along with early intervention work demonstrating the feasibility, short-term benefits (e.g. on QOL) and biologic (mechanistic) changes associated with lifestyle interventions in breast and colon cancer survivors. The impact of the available evidence on clinical practice and the role of large scale clinical trials of energy balance modification with recurrence or survival endpoints (completed, ongoing and planned) will be reviewed, with an emphasis on issues relating to feasibility, cost and the need for embedded correlative research to investigate biologic mechanisms for any survival effects that are identified. Related metformin trials (which target insulin and AMPK/mTOR signaling), notably NCIC MA.32, an adjuvant trial in early breast cancer that will be activated early in 2010, will also be reviewed. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN05-03.