Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery

E. Cash, S. E. Sephton, A. B. Chagpar, D. Spiegel, W. N. Rebholz, L. A. Zimmaro, J. M. Tillie, Firdaus Dhabhar

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n = 43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-ß suggesting tumor invasion/immunosuppression. Factor 2 included IL-1ß, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R2 = .160, p = .038). Patients with elevated CAR also had higher Factor 1 scores (R2 = .293, p = .020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.

Original languageEnglish (US)
Pages (from-to)102-114
Number of pages13
JournalBrain, Behavior, and Immunity
Volume48
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Angiogenesis
  • Biomarker
  • Breast cancer
  • Cortisol
  • Immunosuppression
  • Inflammation
  • Invasion
  • Metastasis
  • Rest-activity
  • Rhythms

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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    Cash, E., Sephton, S. E., Chagpar, A. B., Spiegel, D., Rebholz, W. N., Zimmaro, L. A., Tillie, J. M., & Dhabhar, F. (2015). Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery. Brain, Behavior, and Immunity, 48, 102-114. https://doi.org/10.1016/j.bbi.2015.02.017