Originally published as JCO Early Release 10.1200/JCO.2008.18.9068 on May 26 2009

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Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients

From the Cancer Prevention and Epidemiology Research Programs, Fred Hutchinson Cancer Research Center; Department of Epidemiology, Institute for Public Health Genetics, and Department of Laboratory Medicine, University of Washington, Seattle, WA; Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD; Department of Cancer Etiology, City of Hope National Medical Center, Duarte; Department of Preventive Medicine, University of Southern California, Los Angeles, CA; and Department of Epidemiology and Population Health, University of Louisville, Louisville, KY.

Corresponding author: Cornelia M. Ulrich, MS, PhD, Fred Hutchinson Cancer Center, Cancer Prevention Research Program, 1100 Fairview Ave N, M4-B402, Seattle WA 98109-1024; e-mail: nulrich{at}fhcrc.org.

Purpose Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival.

Patients and Methods We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs.

Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07).

Conclusion Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.

Supported by National Cancer Institute Grants No. N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, U54-CA116847, and R25-CA94880; National Institutes of Health Grant No. M01-RR-00037; University of New Mexico Grant No. NCRR M01-RR-0997; National Institute of Child Health and Human Development Grant No. N01-HD-3-3175; and California Department of Health Services Grant No. 050Q-8709-S1528.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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