Novel Insights Into the Impact of Lifestyle-Based Weight Loss and Metformin on Obesity-Associated Biomarkers in Breast Cancer

Obesity is recognized as a potentially modifiable health condition that is often associated with an abnormal physiologic state that leads to insulin resistance (hyperinsulinemia, dysglycemia, and inflammation), altered adipokines (higher leptin and lower adiponectin), and sex hormones (higher estrogens, androgens, and testosterone), all of which may impact cancer (1–3). Numerous studies have found these obesity-related factors to be associated with worse breast cancer outcomes (4,5). Higher fasting insulin, for example, measured in nondiabetic breast cancer patients at the time of diagnosis, has been associated with worse distant disease–free survival and overall survival (hazard ratio [HR] = 2.05, 95% confidence interval [CI] = 1.16 to 3.62, and HR = 2.57; 95% CI = 1.18 to 5.59, respectively, for upper vs lower quartile) (4). Clinical trials evaluating the survival effects of pharmacologic therapies and lifestyle interventions that lead to improvements in obesity and/or its associated physiology are underway.

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