The effects of a randomized trial of brief forms of stress management on RAGE-associated S100A8/A9 in patients with breast cancer undergoing primary treatment

Cancer. 2019 May 15;125(10):1717-1725. doi: 10.1002/cncr.31965. Epub 2019 Jan 11.


Background: Women with breast cancer (BCa) experience heightened distress, which is related to greater inflammation and poorer outcomes. The s100 protein family facilitates the inflammatory response by regulating myeloid cell function through the binding of Toll-like receptor 4 and the receptor for advanced glycation end products (RAGE). The heterodimer s100A8/A9 RAGE ligand is associated with hastened tumor development and metastasis. Previously, a 10-week stress-management intervention using cognitive behavioral therapy (CBT) and relaxation training (RT) was associated with less leukocyte inflammatory gene expression in patients with BCa; however, its impact on s100A8/A9 was not examined. Because a 10-week intervention may be impractical during primary treatment for BCa, the authors developed briefer forms of CBT and RT and demonstrated their efficacy in reducing distress over 12 months of primary treatment. Here, the effects of these briefer interventions were tested effects on s100A8/A9 levels over the initial 12 months of BCa treatment.

Methods: Postsurgical patients with BCa (stage 0-IIIB) were randomized to a 5-week, group-based condition: CBT, RT, or health education control (HE). At baseline and at 12 months, women provided sera from which s100A8/A9 levels were determined using any enzyme-linked immunosorbent assay.

Results: Participants (mean age ± standard deviation, 54.81 ± 9.63 years) who were assigned to either CBT (n = 41) or RT (n = 38) had significant s100A8/A9 decreases over 12 months compared with those who were assigned to HE (n = 44; F[1,114] = 4.500; P = .036) controlling for age, stage, time since surgery, and receipt of chemotherapy or radiation. Greater increases in stress-management skills from preintervention to postintervention predicted greater reductions in s100A8/A9 levels over 12 months (β = -0.379; t[101] = -4.056; P < .001).

Conclusions: Brief, postsurgical, group-based stress management reduces RAGE-associated s100A8/A9 ligand levels during primary treatment for BCa.

Keywords: RAGE; breast cancer; cognitive behavioral therapy; s100A8/A9; stress management.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / psychology
  • Breast Neoplasms / surgery
  • Calgranulin A / metabolism*
  • Calgranulin B / metabolism*
  • Cognitive Behavioral Therapy / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation Mediators / metabolism
  • Middle Aged
  • Reference Values
  • Relaxation Therapy / methods*
  • Stress, Psychological / diagnosis
  • Stress, Psychological / therapy*
  • Treatment Outcome


  • Calgranulin A
  • Calgranulin B
  • Inflammation Mediators