Metabolic Syndrome, Insulin Resistance, and Inflammation in Breast Cancer: Impact on Prognosis and Adjuvant Interventions

Abstract

The metabolic syndrome, a clinical syndrome that includes central obesity, dyslipidemia, hypertension and glucose intolerance, has been associated with diabetes and cardiovascular disease. Recent evidence links it to breast cancer risk and outcome and suggests that existing adjuvant therapies may exacerbate the syndrome and have reduced efficacy when the syndrome is present. Potential mediators of effects of the syndrome on cancer include insulin/insulin-like growth factor, adipocytokines such as leptin, and markers of inflammation such as interleukins, C-reactive protein, and serum amyloid A. Growing epidemiologic, clinical, and preclinical evidence suggests insulin may be a key mediator. Potential interventions include changes in lifestyle (weight loss, increased physical activity) or pharmacologic approaches. Metformin, a drug commonly used to treat diabetes that reduces the hyperinsulinemia and hyperglycemia associated with the metabolic syndrome, shows promise in epidemiologic, preclinical, and clinical work. Interventions trials involving metformin are underway, including a large adjuvant study by the National Cancer Institute of Canada known as NCIC CTG MA.32.