Effects of Weight Loss and Weight Regain on Circulating Biomarkers in Overweight/Obese Breast Cancer Survivors Enrolled in a Weight Loss Trial in the Rural Midwest

Background: Obesity is associated with worse breast cancer prognosis, however little is known about the level of weight loss required to improve pathway biomarkers. The effects of weight regain on biomarkers are also largely unknown. Methods: Overweight/obese breast cancer survivors enrolled in an 18-month behavioral weight loss trial provided weight and serum biomarkers [leptin, adiponectin, insulin, plasminogen activator inhibitor-1 (PAI-1), IL-6, TNF alpha, and hepatocyte growth factor HGF] at baseline, 6, and 18 months (n = 138). Change in biomarkers over time and by weight loss thresholds were examined. Results: Mean weight loss at 6 months was 13.3 +/- 5.0 kg; from 6 to 18 months, mean regain was 4.0 +/- 5.2 kg. Favorable biomarker modulations were observed at 6 months for leptin, adiponectin, insulin, PAI-1, IL-6, and HGF (P < 0.006 to P < 0.0001). These changes remained significant overall at 18 months despite attenuation in some. Women who lost <10% of baseline weight showed significantly smaller modulation effects for leptin (P < 0.0001), adiponectin:leptin (A/L) ratio (P < 0.0001), PAI-1 (P < 0.001), and insulin (P = 0.003) compared with women who lost >10%. Women who lost >10% observed a significant increase in adiponectin (P < 0.0001), and these women continued to show improved adiponectin from 6 to 18 months despite weight regain. Physical activity contributed additional effects on biomarker change for leptin, A/L, ratio, and PAI-1. Conclusions: These findings are consistent with a clinical target of 10% weight. Impact: Sustained increases in adiponectin likely confer benefits for breast cancer prognosis even with weight regain.