title: Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis.
abstract: BACKGROUND
  A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period.
  
  
  METHODS
  We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters.
  
  
  RESULTS
  In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts.
  
  
  CONCLUSIONS
  Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH, 43210, USA. thornton.84@osu.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Thornton
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Andersen
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000523:psychology; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D003863:Depression / Q000453:epidemiology / Q000276:immunology; D004837:Epinephrine / Q000097:blood; D005221:Fatigue / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007958:Leukocyte Count; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000276:immunology*; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000523:psychology; D009638:Norepinephrine / Q000097:blood; D011788:Quality of Life; D013315:Stress, Psychological / Q000453:epidemiology / Q000276:immunology
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine