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.

Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort

“…The extent to which other comorbid conditions and their associated medications influence BC recurrence and mortality is an area of recent interest. [13,14,26,43–45] Factoring these exposures into BC recurrence prediction may be important and potentially affect follow-up care. In addition, medications that are implicated in the prevention of recurrence may become candidates for use in primary prevention and adjuvant therapy settings.…”

Cooperative Group Cancer Clinical Trials: An NCIC Clinical Trials Group

“…In Mammary.32, observational and pilot data have led to our leadership of a 3500 patient international trial testing the "re-purposing" of metformin as therapy for patients with breast cancer. [12][13][14] In Symptom Control.23, Canadian pilot data are used as a basis to test dexamethasone as an intervention to reduce the pain flare associated with radiation of bone metastases. 15,16 In Head and Neck.6, Canadian contributions to international meta-analyses generated the question to compare hyperfrac-tionated radiation plus a monoclonal antibody with standard chemo-radiation treatment.…”

Cooperative Group Cancer Clinical Trials: An NCIC Clinical Trials Group Perspective

“…In Mammary.32, observational and pilot data have led to our leadership of a 3500 patient international trial testing the "re-purposing" of metformin as therapy for patients with breast cancer. [12][13][14] In Symptom Control.23, Canadian pilot data are used as a basis to test dexamethasone as an intervention to reduce the pain flare associated with radiation of bone metastases. 15,16 In Head and Neck.6, Canadian contributions to international meta-analyses generated the question to compare hyperfractionated radiation plus a monoclonal antibody with standard chemo-radiation treatment.…”