title: Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI). spatel@coh.org.
authors.forename: Sunita K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Wong
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: F Lennie
authors.initials: FL
authors.lastname: Wong
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Elizabeth Crabb
authors.initials: EC
authors.lastname: Breen
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Arti
authors.initials: A
authors.lastname: Hurria
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Christine
authors.initials: C
authors.lastname: Kinjo
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: I Benjamin
authors.initials: IB
authors.lastname: Paz
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Laura
authors.initials: L
authors.lastname: Kruper
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Mortimer
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Palomares
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.affiliation: Department of Population Sciences (SKP, ALW, FLW, MS, CK, MRP), Department of Supportive Care Medicine (SKP), Department of Medical Oncology (AH, IBP, LK, GS, JM, MRP), Department of Surgery (IBP, LK), City of Hope Medical Center and Beckman Research Institute, Duarte, California; Institute of Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL (SB); Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA (ECB, MRI).
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000339:Affect; D000368:Aged; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000523:psychology*; D003071:Cognition; D015897:Comorbidity; D056344:Executive Function; D005221:Fatigue; D005260:Female; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000097:blood / Q000523:psychology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D017698:Postmenopause; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II