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 and 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=0.014). Average DFS was 5.92 years (SD=3.90). Greater 6-12 month CTRA increases predicted shorter 11-year DFS controlling for covariates (p=0.007).

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.

Trial registration: ClinicalTrials.gov NCT01422551.

Keywords: Breast cancer recurrence; Cognitive behavioral stress management; Conserved transcriptional response to adversity; Disease-free survival; Leukocyte gene expression.

Figure 1

CONSORT Diagram; n = 10 participants in the psychoeducational control seminar provided PBMC samples at both T2 and T3; n = 11 participants in the cognitive behavioral stress management condition provided PMBC samples at both T2 and T3.

Figure 2

Group differences in pre- and post-intervention mean CTRA gene expression (N = 51); Adjusted mean CTRA gene expression is depicted controlling for age, disease stage, treatment with chemotherapy, radiation therapy, endocrine therapy, and follow-up time (6 or 12-months). Error bars reflect standard error.

Figure 3

Cox Proportional Hazard Model-predicted survival functions for hypothetical individuals with CTRA change scores falling 1 SD below the mean value on the continuous distribution of CTRA change scores vs. 1 SD above the mean value (and otherwise having identical average or modal values on age, disease stage, treatment with chemotherapy, radiation therapy, and hormone therapy).