J Clin Oncol. 2022 Sep 30. IF: 50.717
Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.
Carroll JE, Nakamura ZM, Small BJ, Zhou X, Cohen HJ, Ahles TA, Ahn J, Bethea TN, Extermann M, Graham D, Isaacs C, Jim HSL, Jacobsen PB, McDonald BC, Patel SK, Rentscher K, Root J, Saykin AJ, Tometich DB, Van Dyk K, Zhai W, Breen EC, Mandelblatt JS.
University of California, Los Angeles, Los Angeles, CA; University of North Carolina-Chapel Hill, Chapel Hill, NC; University of South Florida, Tampa, FL; Georgetown University, Washington, DC; Duke University Medical Center, Durham, NC; Memorial Sloan Kettering Cancer Center, New York, NY; Hackensack University Medical Center, Hackensack, NJ; Moffitt Cancer Center, Tampa, FL; National Cancer Institute, National Institutes of Health, Bethesda, MD; Indiana University School of Medicine, Indianapolis, IN; City of Hope National Medical Center, Los Angeles, CA.
PURPOSE: To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls.
METHODS: English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results.
RESULTS: There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years, range: 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls (P interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance (v controls), with significant interactions with CRP only for the Trails B test.
CONCLUSION: 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.
KEY OBJECTIVE: To determine if higher inflammation predicts later cognitive function in a large, prospective national cohort of older breast cancer survivors and matched noncancer controls followed for up to 60 months.
KNOWLEDGE GENERATED: Older breast cancer survivors had persistently higher C-reactive protein (CRP) levels than controls over time. Survivors with high CRP levels were significantly more likely to report clinically meaningful levels of cognitive problems at later points in time, but this relationship was not seen in controls.
RELEVANCE: Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation plays a mechanistic role in development of cognitive problems. CRP testing could be clinically useful in survivorship care to identify survivors needing intervention to prevent and/or long-term surveillance for cognitive decline.
PMID: 36179271
DOI: 10.1200/JCO.22.00406
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