A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up

Abstract

Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8–15 years post-enrollment. From 1998 to 2005, women (N = 240) 2–10 weeks post-surgery for non-metastatic Stage 0–IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8–15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

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

“…Data were censored on the date of last study contact for women who did not have a breast cancer recurrence or new cancer at time of follow up, were lost to follow-up, or had previously dropped out of the trial. To accommodate data from 7 patients with confirmed breast cancer recurrence but unknown recurrence dates (i.e., interval censored between randomization and end of study/death), our previous analysis of DFS in this trial utilized Weibull Accelerated Failure Time (AFT) models (Stagl et al, 2015). For consistency with those analyses, this study also utilized Weibull AFT models fit using SAS PROC LIFEREG.…”

“…Subsequent analyses of long-term clinical outcomes in the same study found that CBSM is related to improved DFS (Stagl et al, 2015). In the present study, we sought to integrate these molecular and clinical findings with the existing CTRA literature by directly assessing 53 canonical CTRA indicator genes (Fredrickson et al, 2013, 2015) to (a) determine whether CBSM is associated with significant attenuation in CTRA gene expression relative to an active control condition during the first year of primary treatment, and (b) determine whether such attenuation in CTRA gene expression predicts longer DFS over 8–15 years of follow-up.…”

“…Evidence suggests that such interventions may affect long-term clinical outcomes in women with non-metastatic breast cancer (Andersen et al, 2008; Stagl et al, 2015) although these effects have not been consistently observed in the field (Antoni et al, 2006b; Coyne et al, 2007; Daniels and Kissane, 2008; Newell et al, 2002). Andersen et al (2004, 2008) tested a 4-month weekly cognitive-behavioral therapy intervention (with 8 additional monthly maintenance sessions) among women with stage II-III breast cancer, and reported improved psychological symptoms and immune functioning compared to a treatment as usual control group at 4-month follow-up.…”

“…At 8–15 year follow-up (11-year median), women in CBSM had more favorable overall and disease free survival (DFS) compared to women in the control group (Stagl et al, 2015). While studies such as those by Andersen (2008) and Stagl (2015) reveal a link between psychosocial interventions and breast cancer recurrence, more research is needed to identify possible mechanistic pathways. The present study focuses on identifying mechanistic pathways underlying such intervention effects on breast cancer recurrence in a secondary analysis of a previously published trial (Stagl et al, 2015).…”

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

“…Beta adrenergic signalling is central to the intersection between psychosocial stress and cancer, as evidenced in numerous animal models and epidemiological data. A variety of stress reduction techniques have been clinically investigated, including mindfulness meditation [206], cognitive behavioural stress management [207] and even communal singing [208]. Therefore, while the data for an effect on primary tumour growth may be limited in contrast to the results supporting an anti-metastatic effect, there is reason to believe that beta blockade may be beneficial in terms of psychological effects in addition to physical effects on the host environment.…”