title: Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research.
abstract: OBJECTIVE
  Altered levels of cytokines and chemokines may play a role in cancer- and cancer treatment-related cognitive difficulties. In many neurodegenerative diseases, abnormal concentrations of cytokines and chemokines affect neuronal integrity leading to cognitive impairments, but the role of cytokines in chemotherapy-related cognitive difficulties in cancer patients is not well understood. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide plus fluorouracil; AC/CAF) chemotherapy or cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties; because these regimens work by different modes of action, it is possible that they differentially affect cytokine levels.
  
  
  METHODS
  This study examined the relationships between cytokine levels (i.e., IL-6, IL-8, and MCP-1) and type of chemotherapy among 54 early-stage breast cancer patients receiving AC/CAF or CMF. Cytokine levels were assessed at two time-points: prior to on-study chemotherapy cycle 2 (cycle 2) and after two consecutive chemotherapy cycles (prior to on-study cycle 4; cycle 4).
  
  
  RESULTS
  Analyses of variance using cycle 2 levels as a covariate (ANCOVA) were used to determine differences between chemotherapy groups. Levels of IL-6, IL-8, and MCP-1 increased in the AC/CAF group and decreased in the CMF group; the only significant between-group change was in IL-6 (p < 0.05).
  
  
  CONCLUSIONS
  These results, although preliminary based on the small sample size, suggest that AC/CAF chemotherapy is more cytokine inducing than CMF. Future studies should confirm these results and explore the distinct inflammatory responses elicited by different chemotherapy regimens when assessing cognitive function in cancer patients.
authors.affiliation: Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA. michelle_janelsins@urmc.rochester.edu
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Janelsins
authors.forename: Karen M
authors.initials: KM
authors.lastname: Mustian
authors.forename: Oxana G
authors.initials: OG
authors.lastname: Palesh
authors.forename: Supriya G
authors.initials: SG
authors.lastname: Mohile
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Peppone
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Sprod
authors.forename: Charles E
authors.initials: CE
authors.lastname: Heckler
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Roscoe
authors.forename: Alan W
authors.initials: AW
authors.lastname: Katz
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.forename: Gary R
authors.initials: GR
authors.lastname: Morrow
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D013997:Time Factors
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8