The Insulin-like Growth Factor Axis, Adipokines, Physical Activity, and Obesity in Relation to Breast Cancer Incidence and Recurrence

BACKGROUND: Obesity, a risk factor for the development of postmenopausal breast cancer and certain other cancer types, has also been associated with poorer response to cancer therapy and cancer recurrence. The insulin-like growth factor (IGF) axis also influences cancer risk. METHODS: In this commentary, we consider the literature on IGF and its binding proteins and the risk of breast cancer, along with effects of obesity, adipokines, and insulin resistance on breast cancer, and the potential for lifestyle interventions to address weight gain and physical inactivity among at-risk women. RESULTS: Greater body fatness is associated with a higher risk of postmenopausal breast cancer. The association may be explained, in part, by hyperinsulinemia and alterations in adipokines and estrogens. Nutrition, energy balance, and levels of physical activity are determinants of IGF bioactivity. Alterations in the IGF axis can increase cancer risk and progression. Results from epidemiologic studies indicate that higher circulating levels of IGF-I are associated with an increased risk of breast cancer. CONCLUSIONS: Intervention studies are needed to determine how to sustain the positive effects of exercise over time and to identify the optimal mode, intensity, frequency, duration, and timing of exercise for breast cancer survivors, including important subgroups of survivors such as African American and Hispanic women. Future epidemiologic studies of the relationships between the IGF axis and breast cancer should include adequate numbers of African American women, Hispanic women, and other minority women who have been underrepresented in studies completed to date.