Propranolol and survival from breast cancer: a pooled analysis of European breast cancer cohorts

Abstract

BackgroundPreclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all-cause mortality in eight European cohorts.MethodsIncident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all-cause mortality were available for five and eight cohorts, respectively. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality by propranolol and non-selective beta-blocker use. HRs were pooled across cohorts using meta-analysis techniques. Dose–response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis.ResultsThe combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all-cause mortality respectively. Overall, there was no association between propranolol use after diagnosis of breast cancer and breast cancer-specific or all-cause mortality (fully adjusted HR = 0.94, 95% CI, 0.77, 1.16 and HR = 1.09, 95% CI, 0.93, 1.28, respectively). There was little evidence of a dose–response relationship. There was also no association between propranolol use before breast cancer diagnosis and breast cancer-specific or all-cause mortality (fully adjusted HR = 1.03, 95% CI, 0.86, 1.22 and HR = 1.02, 95% CI, 0.94, 1.10, respectively). Similar null associations were observed for non-selective beta-blockers.ConclusionsIn this large pooled analysis of breast cancer patients, use of propranolol or non-selective beta-blockers was not associated with improved survival.

Pathological Crosstalk between Metastatic Breast Cancer Cells and the Bone Microenvironment

“…Additionally, propranolol stabilized p53 levels, and thus increased its phosphorylation resulting in proapoptotic signaling [126]. However, conflicting results were obtained in another clinical study which could not demonstrate an improved survival in breast cancer patients treated with propranolol [127]. By the end of 2016, propranolol was approved in the Orphan Drug Designation by European Medicines Agency (EMA) in soft tissue sarcoma.…”

Propranolol and breast cancer—a work in progress

“…A later meta-analysis by Childers et al did not differentiate between selective and non-selective beta blockers but also reported a significant reduction in breast cancer mortality (HR, 0.50; 95% CI, 0.32-0.80) [ 11 ]. However, a pooled European analysis by Cardwell et al found no evidence for a protective effect of propranolol or beta-blockers in general – although the study did not assess outcomes by stage or primary vs metastatic disease, which may be important [ 12 ].…”

Concurrent new drug prescriptions and prognosis of early breast cancer: studies using the Danish Breast Cancer Group clinical database

“…Propranolol use has been correlated with an 80% decreased rate of breast cancer-specific mortality [55]. However, findings are inconsistent [22,52,57] and imprecise [58].…”