title: Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: A meta-analysis.
abstract: BACKGROUND
  Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear. This meta-analysis aims to consolidate previously published data to identify the risk factors most likely leading to TIC.
  
  
  METHODS
  A search of the MEDLINE literature database using the keywords trastuzumab/Herceptin, risk factors, outcomes, cardiac, cardiotoxicity, cardiomyopathy, LVEF, and chemotherapy was performed. Only prospective/retrospective human studies were included, with additional studies excluded if they reported baseline LVEF > 68%, a cohort of <50 patients, or results that were not stratified based on cardiotoxic events. Pooled odds ratio (OR) and 95% confidence interval (CI) for each potential risk factor were calculated, with heterogeneity of data and samples explored using random-effects modeling.
  
  
  RESULTS
  Data were collected from 17 articles, capturing 6527 patients. Hypertension (OR 1.61, 95% CI 1.14-2.26; P < 0.01), diabetes (OR 1.62; 95% CI 1.10-2.38; P < 0.02), previous anthracycline use (OR 2.14; 95% CI 1.17-3.92; P < 0.02), and older age (P = 0.013) were all shown to be associated with TIC.
  
  
  CONCLUSIONS
  Cardiac performance should be closely monitored in women treated with trastuzumab. Recognizing potential risk factors along with careful attention to symptoms/LVEF measurements could minimize the occurrence of TIC in this population.
authors.affiliation: Department of Internal Medicine, Medical College of Wisconsin Aurora Research Institute, Aurora Health Care Department of Medical Oncology, Aurora Health Care Aurora Cardiovascular Services, Aurora Health Care Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging, Aurora Health Care, Milwaukee, WI.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Jawa
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Perez
authors.forename: Lydia
authors.initials: L
authors.lastname: Garlie
authors.forename: Maharaj
authors.initials: M
authors.lastname: Singh
authors.forename: Rubina
authors.initials: R
authors.lastname: Qamar
authors.forename: Bijoy K
authors.initials: BK
authors.lastname: Khandheria
authors.forename: Arshad
authors.initials: A
authors.lastname: Jahangir
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D066126:Cardiotoxicity; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab / Q000009:adverse effects*
chemical_list: D000068878:Trastuzumab