title: Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data.
abstract: BACKGROUND
  We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.
  
  
  METHODS
  We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.
  
  
  RESULTS
  A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% - 9.4) and 16.4% (95% CI 16.19% - 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 - 75), 71 (66 - 80+), 74.5 (65 - 89), 75 (66 - 81+) and 79.5 (60 - 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 - 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 - 1.87, p < 0.00001).
  
  
  CONCLUSIONS
  Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.
authors.affiliation: a 1 China Medical University-An Nan Hospital, Department of Radiation Therapy , No. 66, Sec. 2, Changhe Rd, Annan Dist, Tainan, Taiwan.
authors.forename: Henry W C
authors.initials: HW
authors.lastname: Leung
authors.affiliation: b 2 China Medical University-An-Nan Hospital, Department of Pharmacy , No. 66, Sec. 2, Changhe Rd, Annan Dist, Tainan, Taiwan +886 63 55 31 11 ; agnes.lf@gmail.com.
authors.forename: Agnes L F
authors.initials: AL
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000453:epidemiology; D066126:Cardiotoxicity / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: breast cancer; cardiac events or toxicity; elderly patient; meta-analysis; trastuzumab