Perioperative Stress, Inflammation, and Cancer Progression: Opportunities for Intervention in Breast and Colorectal Cancer Surgery Utilizing Beta-Adrenergic Blockade and COX-2 Inhibition

Purpose of review: This review explores the blockade of cyclooxygenase (COX)-2/prostaglandin and catecholamine/beta(β)-adrenergic signaling as opportunities to enhance the curative potential of surgical excision of breast and colorectal cancer malignancies. Recent findings: Phase-II randomized placebo-controlled biomarker clinical trials, employing perioperative administration of the COX-2 inhibitor etodolac and the β-adrenergic antagonist propranolol, have shown improved biomarkers associated with both breast and colorectal cancer progression. Tumor epithelial-to-mesenchymal transition (EMT) status and tumor transcription activity levels of GATA-1, GATA-2, EGR3, and STAT-3 were reduced, while anti-cancer immune parameters within the tumor microenvironment improved perioperatively. Increased tumor-associated B cells and NK cells and reduced tumor-associated monocytes were noted. Reduced systemic pro-inflammatory markers IL-6 and CRP were indicated, starting before surgery. Summary: Improved biomarkers of tumor-associated (i) anti-metastatic transcriptional activity, (ii) anti-metastatic immune function, and (iii) reduced systemic inflammatory indices were observed following the combined administration of etodolac and propranolol. These findings support future investigation with larger clinical trials to test long-term cancer outcomes.