Cardioprotective effect of β-adrenoceptor blockade in patients with breast cancer undergoing chemotherapy: follow-up study of heart failure

Circ Heart Fail. 2013 May;6(3):420-6. doi: 10.1161/CIRCHEARTFAILURE.112.000055. Epub 2013 Feb 20.


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.

Methods and 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.

Keywords: anthracyclines; breast cancer; heart failure; toxicity; trastuzumab; β-blocker.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Anthracyclines / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / mortality
  • Cardiotonic Agents / therapeutic use*
  • Comorbidity
  • Female
  • Genes, erbB-2 / physiology
  • Heart Failure / epidemiology
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Heart Failure / prevention & control*
  • Humans
  • Middle Aged
  • Propensity Score
  • Trastuzumab


  • Adrenergic beta-Antagonists
  • Anthracyclines
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cardiotonic Agents
  • Trastuzumab