title: Use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and risk of breast cancer recurrence: a Danish nationwide prospective cohort study.
abstract: OBJECTIVE
  To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort.
  
  
  METHODS
  We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year.
  
  
  RESULTS
  Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3).
  
  
  CONCLUSIONS
  Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. vrelits@gmail.com
authors: Gitte Vrelits
authors: GV
authors: Sørensen
authors: Patricia A
authors: PA
authors: Ganz
authors: Steven W
authors: SW
authors: Cole
authors: Lars A
authors: LA
authors: Pedersen
authors: Henrik Toft
authors: HT
authors: Sørensen
authors: Deirdre P
authors: DP
authors: Cronin-Fenton
authors: Jens Peter
authors: JP
authors: Garne
authors: Peer M
authors: PM
authors: Christiansen
authors: Timothy L
authors: TL
authors: Lash
authors: Thomas P
authors: TP
authors: Ahern
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D003718:Denmark; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries / Q000706:statistics & numerical data; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
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