Elevated C-Reactive Protein May Be Associated With Increased Breast Cancer Risk in Postmenopausal Women Not Using Hormone Therapy


Key Points

  • Higher CRP levels were associated with increased risk of breast cancer in postmenopausal nonusers of hormone therapy.
  • In an analysis including CRP, estradiol, and insulin, higher body mass index was no longer significantly associated with an increased risk of breast cancer.

In a study reported in the Journal of the National Cancer Institute, Gunter and colleagues found that increased levels of the inflammatory marker C-reactive protein (CRP) were associated with increased risk of breast cancer in postmenopausal women not using hormone therapy. No associations of circulating adipokines with risk were observed.

Study Details

The study was a nested case-cohort analysis in the Women’s Health Initiative observational study of postmenopausal women. Baseline plasma samples from 875 women with incident breast cancer and 839 women randomly selected from a subcohort regardless of breast cancer status were assessed for CRP and 7 adipokines (leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor–alpha, hepatocyte growth factor, and plasminogen activator inhibitor-1). Multivariate modeling included established breast cancer risk factors and previously measured levels of estradiol and insulin. A total of 836 women were current hormone therapy users, and 859 were nonusers of hormone therapy.

CRP as Risk Factor

An association between plasma CRP levels and breast cancer risk was found to be dependent on hormone therapy use at baseline (P = .003 for interaction). In multivariate analysis controlling for multiple risk factors including body mass index, estradiol, and insulin, a higher CRP level was associated with an increased breast cancer risk among hormone therapy nonusers (hazard ratio [HR] = 1.67, 95% confidence interval = 1.04–2.68, for 3rd and 4th quartile vs 1st quartile; P = .029 for trend). No significant association was observed among hormone therapy users (HR = 0.90, 95% CI = 0.53–1.53, for 4th vs 1st quartile; P = .509 for trend). None of the seven adipokines was significantly associated with risk of breast cancer.

Decreased Impact of Body Mass Index

In an analysis controlling for risk factors except CRP, insulin, and estradiol, body mass index of 30 vs 25 kg/m2 was significantly associated with an increased breast cancer risk (HR = 1.87, 95% CI = 1.25–2.80, P = .003 for trend). However, in a multivariate model including CRP, insulin, and estradiol, the association of body mass index with breast cancer was attenuated by 115% (HR = 0.91, 95% CI = 0.52–1.61, for ≥ 30 vs < 25 kg/m2; P = .780 for trend).

The investigators concluded: “These data indicate that CRP is a risk factor for postmenopausal breast cancer among hormone therapy nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity–breast cancer relation.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Institutes of Health.

Marc Gunter, PhD, of Imperial College, London, is the corresponding author of the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.