Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.
Title | Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Patel SK, Wong AL, F Wong L, Breen ECrabb, Hurria A, Smith M, Kinjo C, I Paz B, Kruper L, Somlo G, Mortimer JE, Palomares MR, Irwin MR, Bhatia S |
Journal | J Natl Cancer Inst |
Volume | 107 |
Issue | 8 |
Date Published | 2015 Aug |
ISSN | 1460-2105 |
Keywords | Affect, Aged, Biomarkers, Biomarkers, Tumor, Breast Neoplasms, Cognition, Comorbidity, Executive Function, Fatigue, Female, Humans, Inflammatory Breast Neoplasms, Interleukin 1 Receptor Antagonist Protein, Interleukin-6, Memory, Middle Aged, Neuropsychological Tests, Postmenopause, Receptors, Tumor Necrosis Factor, Type II, Surveys and Questionnaires |
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 pro-inflammatory 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. |
DOI | 10.1093/jnci/djv131 |
Alternate Journal | J. Natl. Cancer Inst. |
PubMed ID | 26101331 |
PubMed Central ID | PMC4609551 |
Grant List | P30 AG028748 / AG / NIA NIH HHS / United States P30 CA33572 / CA / NCI NIH HHS / United States P30-AG028748 / AG / NIA NIH HHS / United States R21 CA131878 / CA / NCI NIH HHS / United States R21 CA131878 / CA / NCI NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States |