Psychoneuroimmunology Laboratory, School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel; Stress, Hope and Cope Laboratory, School of Behavioral Sciences, The Academic College of Tel Aviv-Yafo, Tel Aviv, Israel.
Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Brain Behav Immun. 2024 Mar;117:529-540. doi: 10.1016/j.bbi.2024.02.009. Epub 2024 Feb 10.
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.
围手术期应激和炎症信号可能会激活患者肿瘤中的促转移分子过程，从而降低长期生存的可能性。然而，目前尚不清楚术前心理干预是否可以减轻这些影响。在此，40 名诊断为 I-III 期浸润性导管/小叶乳腺癌的女性在手术前 3 周被随机分为 6 周一对一的心理干预组（与医学心理学家进行 6 次会议和每两周打一次电话）和标准护理人员对照组。该干预方案是根据患者的情绪、认知、生理和行为应激反应模式进行个体化定制的，还包括有关医疗治疗和招募社会支持的心理教育。切除的原发性肿瘤进行全基因组 RNA 测序和生物信息学分析，评估预先假设的癌症相关分子特征。自我报告问卷（BSI-18、Hope-18、MSPSS 和应激量表）分别在手术前 3 周（T1）和 1 周（T2）、手术前 1 天（T3）、手术后 1 天（T4）以及手术后 3 周（T5）和 3 个月（T6）进行收集。该干预措施降低了患者的困扰（GSI）、抑郁和躯体化评分（BSI-18：p<0.01，p<0.05，p<0.05；T5 与 T1 相比）。此外，与对照组相比，接受治疗的患者的肿瘤显示：（i）参与肾上腺素能和糖皮质激素信号转导的转录调控途径（CREB、GR）（p<0.001）、促炎信号转导（NFkB）（p<0.01）和促恶性信号转导（ETS1、STAT 和 GATA 家族）（p<0.001，p<0.01，p<0.005）的活性降低；（ii）M1 巨噬细胞极化增加（p<0.05），CD4 T 细胞活性增加（p<0.01）；以及上皮-间充质转化（EMT）特征的意外增加（p<0.005）。这是第一项显示围手术期心理干预对肿瘤促转移分子生物标志物有益影响的随机对照试验。
