Abstract
BackgroundBreast cancer survivors with excess weight are more likely to have negative breast cancer outcomes. Biomarkers related to insulin resistance may help explain this negative association. Weight loss is associated with improvements in insulin sensitivity. Our goal was to identify the impact of a behaviorally based weight loss intervention on indices of insulin resistance.MethodsOverweight, early stage breast cancer survivors who completed initial cancer therapy were enrolled in a 6 month behaviorally based weight loss intervention that included calorie reduction, exercise and behavior modification. Biomarkers related to insulin resistance were obtained at baseline and after the intervention. Results from participants who achieved ≥5% weight loss were compared to those who lost less weight.ResultsDespite not having diabetes as a preexisting diagnosis prior to the study, 69% of all participants were considered to have pre-diabetes or diabetes at baseline based on American Diabetes Association definitions. Participants who achieved ≥5% weight loss had significantly lower fasting insulin, AUC insulin, and insulin resistance as measured by HOMA-IR. Beta cell function decreased as anticipated when insulin resistance improved. Additionally, leptin levels declined.ConclusionsBreast cancer survivors who achieved ≥5% weight loss demonstrated significant improvements in indices of insulin resistance. Despite an exclusion criteria of diabetes at the time of enrolment, a high proportion met criteria for pre-diabetes or diabetes at baseline. Pre-diabetes appears to be under recognized in overweight breast cancer survivors. Behaviorally based weight loss interventions can result in weight loss and improvements in biomarkers related to breast cancer outcomes and additionally may decrease the chance of developing diabetes.Trial registrationNCT01482702 4/12/2010 (retrospectively registered). https://clinicaltrials.gov/ct2/show/NCT01482702?term=Dittus&rank=4
Highlights
Breast cancer survivors with excess weight are more likely to have negative breast cancer outcomes
It is estimated that 66% of breast cancer survivors are overweight or obese [1]; obese breast cancer survivors have a 30% higher risk of breast cancer and overall mortality compared to normal weight women [2, 3]
In pre-clinical research insulin resistance is associated with pathways implicated in cancer development and progression including the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K) pathway [6]
Summary
Breast cancer survivors with excess weight are more likely to have negative breast cancer outcomes. Biomarkers related to insulin resistance may help explain this negative association. Weight loss is associated with improvements in insulin sensitivity. Epidemiologic studies suggest that each 5 kg weight gain increment is Insulin resistance and related pathways represent a plausible mechanistic explanation for the relationship between excess weight and negative breast cancer outcomes [5]. Epidemiologic evidence identifies a two-fold increase in the risk of breast cancer recurrence. Dittus et al BMC Cancer (2018) 18:351 and a three-fold increased risk of death in breast cancer survivors with the highest fasting insulin levels [5]. Adipose-derived metabolic hormones, such as the adipokines leptin and adiponectin, modulate insulin sensitivity, activate NFkB and the mTOR pathway and are associated with breast cancer risk [7, 8]
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