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

Tsipi Hanalis-Miller, Itay Ricon-Becker, Nahida Sakis, Estherina Trachtenberg, Frida Ohayon, Sonya Wadhawker, Yehudit Birnboim, Ada Magen, Eran Sharon, Ricardo Tarrasch, Gil Goldzweig, Steve W. Cole, Rebecca Jacoby, Shamgar Ben-Eliyahu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)529-540
Number of pages12
JournalBrain, Behavior, and Immunity
Volume117
DOIs
StatePublished - Mar 2024

Funding

FundersFunder number
IMS, Israel
Israel Cancer Research Fund
Israel Science Foundation
Tel Aviv University

    Keywords

    • Breast cancer
    • Gene expression
    • Metastases
    • NFkB
    • Perioperative
    • Prevention
    • Stress-management

    Fingerprint

    Dive into the research topics of 'Peri-operative individually tailored psychological intervention in breast cancer patients improves psychological indices and molecular biomarkers of metastasis in excised tumors'. Together they form a unique fingerprint.

    Cite this