Insulin, Estrogen, Inflammatory Markers and Risk of Benign Proliferative Breast Disease.

Publication Type:

Journal Article


Cancer research (2014)


2014, May 2014, Public Health Sciences Division


Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up and they were matched to 1321 controls. Levels of insulin, estradiol, C-reactive protein (CRP) and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate odds ratios for the association of each factor with BPBD risk. Among non-users of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile=1.80; 95%CI=1.16-2.79; ptrend=0.003) as were levels of estradiol (OR for highest vs. lowest tertile=1.89; 95%CI=1.26-2.83; ptrend=0.02) and CRP (OR for highest vs. lowest quartile=2.46; 95%CI=1.59-3.80; ptrend<0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile=0.47; 95%CI=0.31-0.71; ptrend<0.001). These associations persisted after mutual adjustment but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin and inflammation pathways are associated with the early stages of breast cancer development.