title: Beta blockers and breast cancer mortality: a population- based study.
abstract: OBJECTIVE
  Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality.
  
  
  METHODS
  Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed.
  
  
  RESULTS
  Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers.
  
  
  CONCLUSIONS
  The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.
authors.affiliation: Trinity College, University of Dublin, Dublin, Ireland. barront@tcd.ie
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Barron
authors.forename: Roisin M
authors.initials: RM
authors.lastname: Connolly
authors.forename: Linda
authors.initials: L
authors.lastname: Sharp
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bennett
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D001262:Atenolol / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality* / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D015994:Incidence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D011336:Probability; D011433:Propranolol / Q000627:therapeutic use; D012044:Regression Analysis; D015398:Signal Transduction
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol