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- Title
Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.
- Authors
Patel, Sunita K.; Wong, Andrew L.; Wong, F. Lennie; Breen, Elizabeth Crabb; Hurria, Arti; Smith, Mackenzie; Kinjo, Christine; Paz, I. Benjamin; Kruper, Laura; Somlo, George; Mortimer, Joanne E.; Palomares, Melanie R.; Irwin, Michael R.; Bhatia, Smita
- Abstract
Background: Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by proinflammatory cytokines. Methods: One hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided. Results: Memory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively). Conclusion: An association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.
- Subjects
COGNITION disorders research; BREAST cancer patients; CANCER immunology; CYTOKINES; NEUROPSYCHOLOGICAL tests; INTERLEUKIN-6; INTERLEUKIN-1 receptor antagonist protein; TUMOR necrosis factor receptors
- Publication
JNCI: Journal of the National Cancer Institute, 2015, Vol 107, Issue 8, p1
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djv131