title: Cardioprotective effect of β-adrenoceptor blockade in patients with breast cancer undergoing chemotherapy: follow-up study of heart failure.
abstract: BACKGROUND
  Chemotherapy with trastuzumab and anthracycline is associated with incident heart failure (HF) in patients with breast cancer. We hypothesized that continuous incidental use of β-blocker agents (BB) was protective against HF in patients without established structural heart disease who were receiving trastuzumab and anthracycline.
  
  
  RESULTS
  We identified 920 consecutive patients with breast cancer (age 52.3±11.0 years) with normal ejection fraction before receiving trastuzumab and anthracycline therapy at our institution between 2005 and 2010. Using a propensity score and a greedy 5 to 1 digit-matching algorithm, 106 of these patients on continuous BB during cancer treatment were matched with 212 patients from the same pool with similar characteristics but not on continuous BB. During a median follow-up of 3.2±2.0 years, 32 incident HF admissions were identified in these 318 patients with breast cancer, whereas 28 cancer-related (noncardiac) deaths occurred before any incident HF. Cumulative incidence regression models and cause-specific hazards of new HF events were estimated from competing risk Cox models of time-dependent covariates. Although trastuzumab therapy showed significant association with incident HF, independent of anthracycline-related cardiotoxicity (hazard ratio, 9.0; 95% confidence interval, 3.0-27.0; P<0.0001), continuous use of BB was associated with lower risk of new HF events (hazard ratio, 0.2; 95% confidence interval, 0.1-0.5; P=0.003).
  
  
  CONCLUSIONS
  Coincidental, continuous use of BB is associated with lower incidence of HF in patients with breast cancer and normal baseline ejection fraction in a competing risk framework, and after matching for demographics, clinical, and cancer-related treatment characteristics. Prospective randomized clinical trials to validate these findings are warranted.
authors: Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Sinziana
authors: S
authors: Seicean
authors: Andreea
authors: A
authors: Seicean
authors: Nima
authors: N
authors: Alan
authors: Juan Carlos
authors: JC
authors: Plana
authors: G Thomas
authors: GT
authors: Budd
authors: Thomas H
authors: TH
authors: Marwick
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D015897:Comorbidity; D005260:Female; D018734:Genes, erbB-2 / Q000502:physiology; D006333:Heart Failure / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D057216:Propensity Score; D000068878:Trastuzumab
chemical_list: D000319:Adrenergic beta-Antagonists; D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D000068878:Trastuzumab
keywords: anthracyclines; breast cancer; heart failure; toxicity; trastuzumab; β-blocker