Peri-operative individually tailored psychological intervention in breast cancer patients improves psychological indices and molecular biomarkers of metastasis in excised tumors.

Perioperative stress and inflammatory signaling can invigorate pro-metastatic molecular processes in patients' tumors, potentially worsening long-term survival. Yet, it is unknown whether pre-operative psychotherapeutic interventions can attenuate such effects. Herein, three weeks before surgery, forty women diagnosed with stage I-III invasive ductal/lobular breast carcinoma were randomized to a 6-week one-on-one psychological intervention (6 meetings with a medical psychologist and bi-weekly phone calls) versus standard nursing-staff-attention. The intervention protocol was individually tailored based on evaluation of patients' emotional, cognitive, physiological, and behavioral stress response-patterns, and also included psychoeducation regarding medical treatments and recruitment of social support. Resected primary tumors were subjected to whole-genome RNA sequencing and bioinformatic analyses, assessing a priori hypothesized cancer-relevant molecular signatures. Self-report questionnaires (BSI-18, Hope-18, MSPSS, and a stress-scale) were collected three (T1) and one (T2) week before surgery, a day before (T3) and after (T4) surgery, and three weeks (T5) and 3-months (T6) following surgery. The intervention reduced distress (GSI), depression, and somatization scores (BSI-18: p < 0.01, p < 0.05, p < 0.05; T5 vs. T1). Additionally, tumors from treated patients (vs. controls) showed: (i) decreased activity of transcription control pathways involved in adrenergic and glucocorticoid signaling (CREB, GR) (p < 0.001), pro-inflammatory signaling (NFkB) (p < 0.01), and pro-malignant signaling (ETS1, STAT and GATA families) (p < 0.001, p < 0.01, p < 0.005); (ii) increased M1 macrophage polarization (p < 0.05), and CD4+ T cell activity (p < 0.01); and an unexpected increase in epithelial-to-mesenchymal-transition (EMT) signature (p < 0.005). This is the first randomized controlled trial to show beneficial effects of a psychological perioperative intervention on tumor pro-metastatic molecular biomarkers.

Increased sympathetic modulation in breast cancer survivors determined by measurement of heart rate variability.

Experimental and clinical studies have shown that the sympathetic nervous system (SNS) stimulates cancer progression and reduces the efficacy of oncological treatment. These effects may be reduced by pharmacological and psychotherapeutical approaches attenuating SNS tone. Therefore, it is necessary to identify those cancer survivors whose sympathetic modulation is excessively increased. For determination of SNS modulation, non-invasive method of heart rate variability (HRV) is widely used. In our study, HRV was determined from 5-min heartbeat recordings in healthy volunteers and in women with benign or malignant breast neoplasias, both in newly diagnosed patients and in women after initial treatment. We showed impaired cardio-vagal regulation in breast cancer patients (linear methods) and also found the increased sympathetic modulation indicated by the non-linear (the symbolic dynamics 0V%) parameter. This non-linear HRV analysis seems to be more sensitive than the linear one, indicating significant differences also in survivors after initial therapy in comparison to healthy controls. The lower sample entropy revealed reduced complexity in heart rate control in both breast cancer survivors groups. These findings suggest that HRV detection represents an inexpensive, easy, and reliable method for identification of those patients with breast cancer whose sympathetic modulation is significantly increased and in which the interventions, aimed at normalizing the balance in the autonomic nervous system (e.g. psychotherapy, biofeedback, treatment by ß-blockers) may be the most effective.

The Effect of Pre-operative Psychological Interventions on Psychological, Physiological, and Immunological Indices in Oncology Patients: A Scoping Review.

Introduction: The stressful pre-operative period exerts a profound impact on psychological, physiological and immunological outcomes. Oncological surgeries, in particular, elicit significantly higher stress responses than most other surgeries. Managing these responses through psychological interventions may improve long-term outcomes. The purpose of the current research was to review studies that have explored pre-operative psychological interventions in cancer patients in order to map the types of current interventions and provide an initial assessment of whether these interventions improved psychological, physiological, and/or immunological indices as well as long-term cancer outcomes. Methods: A systematic literature search for studies that included pre-operative psychological interventions in oncology patients was conducted, using the databases PubMed and Web of Science. Inclusion criteria included studies pertaining to oncological surgery in adults, study designs that included a clearly defined pre-operative psychological intervention and control group. Results: We found 44 studies, each using one of the following interventions: psychoeducation, cognitive interventions, relaxation techniques, integrated approaches. All the studies reported improved immediate post-operative psychological, physiological, and/or immunological outcomes. Only a few studies addressed long-term cancer outcomes, and only one reported improved survival. Conclusions: Research on pre-operative interventions with cancer patients is missing systematic methods. Studies provide varying results, which makes it difficult to compare them and reach reliable conclusions. There is considerable heterogeneity in the literature regarding the specific intervention used, the timing of intervention, the characteristics of the patients studied and the outcome measures. In order to improve research in this field, including the measurement of long-term outcomes, we suggest some steps that should be taken in further research.

Individual stress response patterns: Preliminary findings and possible implications.

BACKGROUND: Research on stress occupied a central position during the 20th century. As it became evident that stress responses affect a wide range of negative outcomes, various stress management techniques were developed in attempt to reduce the damages. However, the existing interventions are applied for a range of different stress responses, sometimes unsuccessfully. OBJECTIVE: The aim of this study was to examine whether there are specific clusters of stress responses representing interpersonal variation. In other words, do people have dominant clusters reflecting the different aspects of the known stress responses (physiological, emotional, behavioral, and cognitive)? METHODS: The researchers derived a measure of stress responses based on previous scales and used it in two studies in order to examine the hypothesis that stress responses can be grouped into dominant patterns according to the type of response. RESULTS: The results of Study 1 revealed four distinctive response categories: psychological (emotional and cognitive), physiological gastro, physiological muscular, and behavioral. The results of Study 2 revealed five distinctive response categories: emotional, cognitive, physiological gastro, physiological muscular, and behavioral. CONCLUSION: By taking into consideration each person's stress response profile while planning stress management interventions and then offering them a tailored intervention that reduces the intensity of these responses, it might be possible to prevent further complications resulting in a disease (physical or mental).

Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of ß-adrenergic and cyclooxygenase 2 signaling.

Evidence suggests that excess perioperative activation of the sympathetic nervous system and the consequent release of catecholamines (ie, epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate prometastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long-term cancer outcomes nonproportionally to its short duration (days to weeks). Then, it analyzes the various mechanisms via which the excess release of catecholamines can facilitate the progression of cancer metastases in this context by directly affecting the malignant tissues and by regulating, via indirect pathways, immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically. In addition, this review addresses the need to supplement ß-adrenoreceptor blockade with cyclooxygenase 2 inhibition, especially during surgery and shortly thereafter, because similar mechanisms are simultaneously activated by surgery-induced inflammatory responses. Importantly, this review presents translational and clinical evidence showing that perioperative ß-adrenoreceptor blockade and cyclooxygenase 2 inhibition can reduce the prometastatic process and cancer recurrence, and the clinical feasibility and safety of this approach are demonstrated as well. Lastly, alternative psychophysiological approaches to the use of ß-adrenergic blockers are presented because a substantial portion of patients have medical contraindications to this pharmacological treatment. The adaptation of existing psychophysiological interventions to the perioperative period and principles for constructing new approaches are discussed and exemplified. Overall, pharmacobehavioral interventions, separately or in combination, could transform the perioperative timeframe from being a prominent facilitator of metastatic progression to an opportunity for arresting or eliminating residual disease, potentially improving long-term survival rates in cancer patients.