Stress management, leukocyte transcriptional changes and breast cancer recurrence in a randomized trial: An exploratory analysis

Abstract

Purpose Cognitive behavioral stress management (CBSM) is an empirically-validated group-based psychosocial intervention. CBSM is related to decreased self-reported indicators of psychological adversity during breast cancer treatment and greater disease-free survival (DFS) vs. a control condition. This study examined relationships between CBSM, DFS, and a potential biobehavioral pathway linking these variables in breast cancer patients through a gene expression composite representing the leukocyte conserved transcriptional response to adversity (CTRA). Design Women with stage 0-IIIb breast cancer completed questionnaires and provided blood samples post-surgery. Participants were randomized to 10-week group-based CBSM or a psychoeducation control group and followed at 6 months, 12 months, and median 11 years. In total, 51 participants provided blood data for longitudinal analyses (CBSM n = 28; Control n = 23). Mixed model analyses examined CBSM effects on 6–12 month changes in CTRA expression (53 indicator genes representing pro-inflammatory, anti-viral and antibody production signaling). Cox regression models assessed the relationship between 6–12 month changes in CTRA expression and 11-year DFS. Results Patients randomized to CBSM showed attenuated 6–12 month change in CTRA gene expression, whereas patients randomized to control showed increased CTRA expression (p = 0.010). Average DFS was 5.92 years (SD = 3.90). Greater 6–12 month CTRA increases predicted shorter 11-year DFS controlling for covariates (p = 0.023). Conclusions CBSM attenuated CTRA gene expression during the initial year of breast cancer treatment. In turn, greater increases in CTRA gene expression predicted shorter long-term DFS. These findings identify a biobehavioral oncology pathway to examine in future work.

Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behavior

“…Second, the health significance of the present genomic findings needs to be interpreted with caution until more is known about the quantitative relationship between CTRA gene expression and disease risk in healthy populations such as this one. Even though prosocial behavior causally influenced CTRA expression in this study, and CTRA expression has been linked elsewhere to clinical health outcomes (e.g., Antoni et al, 2016;Cole et al, 2015a;Knight et al, 2016), this study contains no measures of clinical health outcomes. In addition, although we postulate that our prosocial behavior intervention informs the understanding of the link between relationships and health, we did not directly measure whether our manipulation led to objective changes in participants' relationships.…”

Emotion and biological health: the socio-cultural moderation

“…As noted by Finch in his major review on the topic [11], ‘later life dysfunctions of the vasculature, brain, and cell growth may be traced to prodromal (subclinical) inflammatory changes from early in life (page 6).’ Recent work has also provided direct empirical support for the link between CTRA and health outcomes [21 • ,22]. …”

Social Stress Mobilizes Hematopoietic Stem Cells to Establish Persistent Splenic Myelopoiesis

“…This profile is consistent with the “conserved transcriptional response to adversity” (CTRA) that has been observed in leukocyte profiles of individuals experiencing chronic stress (Cole et al, 2011, 2015a; Powell et al, 2013; Miller et al, 2014). CTRA and stress-induced myelopoiesis are major predictors of disease outcomes, including atherosclerosis (Tawakol et al, 2017; Heidt et al, 2014), cancer (Antoni et al, 2016), and anxiety disorders (Kohrt et al, 2016; Wohleb et al, 2015). These observations demonstrate that immune adaptations to chronic stress are important mediators of the social determinants of health.…”