Markers of Inflammation and Incident Breast Cancer Risk in the Women's Health Study

Am J Epidemiol. 2018 Apr 1;187(4):705-716. doi: 10.1093/aje/kwx250.


Chronic inflammation may be a risk factor for the development and progression of breast cancer, yet it is unknown which inflammatory biomarkers and pathways are especially relevant. The present study included 27,071 participants (mean age = 54.5 years) in the Women's Health Study who were free of cancer and cardiovascular disease at enrollment (1992-1995), with baseline measures of 4 inflammatory biomarkers: high-sensitivity C-reactive protein, fibrinogen, N-acetyl side-chains of acute phase proteins, and soluble intercellular adhesion molecule-1. We used Cox proportional hazards regression models to evaluate associations between baseline concentrations of biomarkers and incident breast cancer, and adjusted for baseline and time-varying factors such as age and body mass index. Self-reported invasive breast cancer was confirmed against medical records for 1,497 incident cases (90% postmenopausal). We observed different patterns of risk depending on the inflammatory biomarker. There was a significant direct association between fibrinogen and breast cancer risk (for quintile 5 vs. quintile 1, adjusted hazard ratio = 1.25, 95% confidence interval: 1.03, 1.51; P for trend = 0.01). In contrast, soluble intercellular adhesion molecule-1 was inversely associated with breast cancer (for quintile 5 vs. quintile 1, adjusted hazard ratio = 0.79, 95% confidence interval: 0.66, 0.94; P for trend = 0.02). N-acetyl side-chains of acute phase proteins and high-sensitivity C-reactive protein were not associated with breast cancer. The complex association of chronic inflammation and breast cancer may be considered when formulating anti-inflammatory cancer prevention or intervention strategies.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers
  • Body Mass Index
  • Breast Neoplasms / blood*
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / pathology
  • C-Reactive Protein / biosynthesis
  • Chronic Disease
  • Female
  • Fibrinogen / biosynthesis
  • Health Behavior
  • Humans
  • Inflammation / blood*
  • Inflammation / epidemiology*
  • Inflammation Mediators / blood*
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Middle Aged
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • Risk Factors
  • Women's Health


  • Biomarkers
  • Inflammation Mediators
  • Intercellular Adhesion Molecule-1
  • Fibrinogen
  • C-Reactive Protein