Energy balance, insulin resistance biomarkers, and breast cancer risk

American women are five times more likely to be at risk for breast cancer than women from Asian countries. Epidemiologic studies have linked energy balance to an increased risk of breast cancer, yet few studies have investigated potential mediators of this association with Chinese women. We examined the above association by blood levels of insulin-like growth factors (IGFs), binding proteins, and C-peptide in the Shanghai Breast Cancer Study (SBCS), a case-control study conducted among 1,459 breast cancer cases and 1,556 healthy Chinese women from 1996 and 1998.

In-person surveys were used to collect data on energy intake, anthropometric measures, exercise/sport activity, and occupational activity. The present analyses consisted of 397 cases and 397 controls whose blood samples were measured for levels of IGFs, insulin growth-factor binding protein 3 (IGFBP-3), C-peptide, and the relationship with physical activity status, total energy intake, and body fat distribution.

Body mass index (BMI) and waist-to-hip ratio (WHR) were significantly positively correlated with IGFBP-3 and C-peptide. Adult exercise/sport activity was significantly negatively correlated with insulin-like growth factor 1 (IGF-I). C-peptide levels increased with increasing quartiles of WHR (p for trend<0.01). Additional analyses were performed to evaluate whether the association of energy balance measures with breast cancer risk changed after adjustment for IGFs, IGFBP-3, and C-peptide biomarkers. The associations attenuated, but none of them changed substantially.

Insulin resistance biomarkers may partially explain the association between positive energy balance and breast cancer risk, but future studies are needed to identify the underlying complex biological mechanisms of action for breast cancer prevention.