Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease

Chelsea Catsburg, Marc J. Gunter, Chu Chen, Michele L. Cote, Geoffrey C. Kabat, Rami Nassir, Lesley Tinker, Jean Wactawski-Wende, David L. Page, Thomas E. Rohan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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 with in the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 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 ORs for the association of each factor with BPBD risk. Among nonusers 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% confidence interval, 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.

Original languageEnglish (US)
Pages (from-to)3248-3258
Number of pages11
JournalCancer research
Issue number12
StatePublished - Jun 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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