title: Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case-control study.
abstract: BACKGROUND
  The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers.
  
  
  METHODS
  Patients with breast cancer were enrolled in a trial of adjuvant AI therapy. Changes in pain and function during therapy were assessed prospectively. We selected 30 cases with AIMSS and 22 controls without AIMSS, matched for demographics and prior therapy. Serum samples collected at baseline and during treatment were assayed for multiple inflammatory cytokines and lipid mediators using multiplex assays.
  
  
  RESULTS
  Before AI therapy, mean serum concentrations of 6 of 36 assayed factors were statistically significantly lower in cases than controls (all P<0.003). No statistically significant changes during AI therapy relative to pre-treatment were observed between cases and controls for any of the inflammatory markers tested.
  
  
  CONCLUSIONS
  AIMSS is probably not associated with a systemic inflammatory response. Pre-treatment cytokine levels may predict for development of AIMSS.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, 300 North Ingalls, North Ingalls Building 3A04, Ann Arbor, MI 48109-5419, USA. norahh@med.umich.edu
authors.forename: N L
authors.initials: NL
authors.lastname: Henry
authors.forename: D
authors.initials: D
authors.lastname: Pchejetski
authors.forename: R
authors.initials: R
authors.lastname: A'Hern
authors.forename: A T
authors.initials: AT
authors.lastname: Nguyen
authors.forename: P
authors.initials: P
authors.lastname: Charles
authors.forename: J
authors.initials: J
authors.lastname: Waxman
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: A M
authors.initials: AM
authors.lastname: Storniolo
authors.forename: D F
authors.initials: DF
authors.lastname: Hayes
authors.forename: D A
authors.initials: DA
authors.lastname: Flockhart
authors.forename: V
authors.initials: V
authors.lastname: Stearns
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D004967:Estrogens / Q000172:deficiency; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced*; D017698:Postmenopause; D013577:Syndrome; D013629:Tamoxifen / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D001952:Bridged-Ring Compounds; D016207:Cytokines; D004967:Estrogens; D043823:Taxoids; D013629:Tamoxifen; C080625:taxane; C056516:exemestane