C-Reactive Protein Level and Cognitive Function in Breast Cancer Survivors Aged 60 and Older

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As reported in the Journal of Clinical Oncology by Carroll et al, an analysis from the Thinking and Living with Cancer Study has shown higher levels of C-reactive protein (CRP) at baseline and during follow-up among women with stage 0 to III breast cancer diagnosed at age ≥ 60 years vs controls, with higher levels among survivors being associated with poorer cognitive performance.

Study Details

The study included 400 breast cancer survivors and 329 noncancer controls enrolled at sites in the United States between September 2010 and March 2020. Controls were frequency-matched at enrollment at each study site to survivors for age, education level, and race. Women with dementia, neurologic disorders, and other cancers were excluded from the study.

Assessments occurred prior to systemic therapy/enrollment (baseline) and at annual visits for up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and neuropsychological testing. CRP analysis used natural log (ln)-transformed CRP levels at each visit. Analyses were adjusted for age, race, study site, cognitive reserve, obesity, and comorbidities.

Key Findings

The majority of survivors had stage I disease (60.9%) and estrogen receptor–positive tumors (87.6%).

Among participants with baseline samples, nontransformed CRP levels of ≥ 3 mg/L were found in 42.4% of survivors vs 26.1% of controls (P < .001).

Survivors had significantly higher adjusted mean ln-CRP vs controls at baseline, as well as at 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted poorer cognitive function at subsequent visits on FACT-Cog among survivors (P = .040) but not among controls (P = .795; P = .014 for interaction). These effects were unchanged in analyses including depression and anxiety. Overall, as survivor nontransformed CRP levels increased from 1.0 to 3.0 to 10.0 mg/L, adjusted FACT-Cog scores were 5.2, 9.5, and 14.2 points lower, respectively, vs controls.

Adjusted ln-CRP levels did not predict subsequent scores for survivors or controls in neuropsychological test domains. Survivors had small decreases in neuropsychological test performance vs controls, with a significant interaction with CRP observed for the Trails B test.

The investigators concluded, “Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.”

Judith E. Carroll, PhD, of the Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health and the National Cancer Institute. For full disclosures of the study authors, visit

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