Psychological and/or pharmacological short perioperative interventions to reduce cancer recurrence: A planned randomized clinical trial in breast cancer patients

Abstract

Several surgery-related processes, including sympathetic-activation and inflammation, may promote metastatic progression. In two recent biomarkers clinical trials in breast (n = 38) and colorectal (n = 34) cancer patients, a 5-day pre-operative beta-adrenergic blockade and COX2-inhibition (employing propranolol and etodolac for 11-perioperative days) significantly reduced pro-metastatic markers in the excised tumor, presumably through mitigating stress. However, due to medical contraindications, less than 50% of patients were eligible for this treatment. Thus, in a phase-II clinical trial, we plan to compare a perioperative psychological intervention to the above perioperative pharmacological treatment. Psychological intervention layout: Starting 3 weeks before surgery, a six-week treatment will include five individual sessions around routine clinic visits. Between sessions, bi-weekly phone support will be provided by a psychologist. A stress-management intervention tailored for each woman will address the following domains: (i) physiological (ii) cognitive, and (iii) emotional aspects of stress. Additionally, (iv) medical psycho-education, and (v) perceived social support will be addressed. A 2X2 design will be used: Placebo, Pharmacological, Psychological + Placebo, or both treatments. Additionally, patients with contra-indications to pharmacological treatment will be randomized to Placebo vs Psychological treatment + Placebo (n = 30 in each of the 6 groups). Short-term outcomes: tumor mRNA profiling, self-report questionnaires (e.g., BSI 18), Heart-Rate-Variability, circadian saliva cortisol. The combined approach is hypothesized to be optimal. Future studies may assess long-term clinical outcomes such as disease progression or survival.