Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.

TitleInflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.
Publication TypeJournal Article
Year of Publication2015
AuthorsPatel 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
JournalJ Natl Cancer Inst
Date Published2015 Aug
KeywordsAffect, 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

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.

Alternate JournalJ. Natl. Cancer Inst.
PubMed ID26101331
PubMed Central IDPMC4609551
Grant ListP30 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