Blocking the beta-adrenergic and COX-2 pathways in patients during the perioperative period may inhibit cellular and molecular pathways associated with metastasis and disease recurrence in early stage breast cancer, according to a study published in Clinical Cancer Research.

Previous studies have demonstrated that surgery triggers the beta-adrenergic and COX-2 pathways, which may lead to the formation of new metastases and poor long-term outcomes.

For this phase 2 study (ClinicalTrials.gov Identifier: NCT00502684), 38 women with early-stage breast cancer were randomly assigned to receive placebo or propranolol and etodolac for 11 days, starting 5 days before surgery. The researchers assessed excised tumors and blood samples for prometastatic biomarkers.

The results of the study demonstrated that patients pretreated with study medications had significantly lower epithelial-to-mesenchymal transition, decreased activity of prometastatic/proinflammatory transcription factors (ie, GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer, and activator of transcription-3/STAT-3), and reduced tumor-infiltrating monocytes with increased tumor-infiltrating B cells, which are outcomes that have been previously linked to reduced tumor progression.

Treatment also led a significantly reduced increase in presurgical serum IL6 and C-reactive protein, abrogated perioperative declines in stimulated IL12 and IFNɣ production, decreased postoperative mobilization of CD16 classical monocytes, and enhanced expression of CD11a on circulating natural killer cells, all factors that have been associated with progression and poor prognosis. 

The authors conclude saying that “these findings provide a biological rationale for future clinical trials to assess the impact of this easily implemented, safe, and inexpensive treatment regimen on long-term clinical outcomes (eg, overall and recurrence-free survival).”

Reference

1. Shaashua L, Shabat-Simon M, Haldar R, et al. Perioperative COX-2 and β-adrenergic blockade improves metastatic biomarkers in breast cancer patients in a phase-II randomized trial [published online May 10, 2017]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-17-0152