title: Trastuzumab-related cardiotoxicity among older patients with breast cancer.
abstract: OBJECTIVE
  The use of trastuzumab in the adjuvant setting improves outcomes but is associated with cardiotoxicity manifested as congestive heart failure (CHF). The rates and risk factors associated with trastuzumab-related CHF among older patients are unknown.
  
  
  METHODS
  Breast cancer patients at least 66 years old with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005 and 2009, and treated with chemotherapy were identified in the SEER-Medicare and in the Texas Cancer Registry-Medicare databases. The rates and risk factors associated with CHF were evaluated. Chemotherapy, trastuzumab use, comorbidities, and CHF were identified using International Classification of Diseases, version 9, and Healthcare Common Procedure Coding System codes. Analyses included descriptive statistics and Cox proportional hazards models.
  
  
  RESULTS
  In total, 9,535 patients were included, of whom 2,203 (23.1%) received trastuzumab. Median age of the entire cohort was 71 years old. Among trastuzumab users, the rate of CHF was 29.4% compared with 18.9% in nontrastuzumab users (P < .001). Trastuzumab users were more likely to develop CHF than nontrastuzumab users (hazard ratio [HR], 1.95; 95% CI, 1.75 to 2.17). Among trastuzumab-treated patients, older age (age > 80 years; HR, 1.53; 95% CI, 1.16 to 2.10), coronary artery disease (HR, 1.82; 95% CI, 1.34 to 2.48), hypertension (HR, 1.24; 95% CI, 1.02 to 1.50), and weekly trastuzumab administration (HR, 1.33; 95% CI, 1.05 to 1.68) increased the risk of CHF.
  
  
  CONCLUSIONS
  In this large cohort of older breast cancer patients, the rates of trastuzumb-related CHF are higher than those reported in clinical trials. Among patients treated with trastuzumab, those with cardiac comorbidities and older age may be at higher risk. Further studies need to confirm the role that the frequency of administration plays in the development of trastuzumab-related CHF.
authors.affiliation: From The University of Texas MD Anderson Cancer Center.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chavez-MacGregor
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiangong
authors.initials: J
authors.lastname: Niu
authors.forename: Linda
authors.initials: L
authors.lastname: Elting
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Smith
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Giordano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D006278:Medicare / Q000706:statistics & numerical data; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012307:Risk Factors; D018426:SEER Program / Q000706:statistics & numerical data; D000068878:Trastuzumab; D014481:United States / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab