title: β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.
abstract: The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer.
authors.affiliation: Department of Surgery, Pinnacle Health System, Harrisburg, PA.
authors.forename: W Kurtis
authors.initials: WK
authors.lastname: Childers
authors.affiliation: Departments of Surgery and Public Health Sciences, Penn State College of Medicine, Hershey, PA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hollenbeak
authors.affiliation: Department of Internal Medicine, Pinnacle Health System, Harrisburg, PA. Electronic address: PCheriyath@pinnaclehealth.org.
authors.forename: Pramil
authors.initials: P
authors.lastname: Cheriyath
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology*; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology*
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: Breast cancer metastasis; Breast cancer recurrence; Meta-analysis; β-adrenergic receptors; β-blockers