title: Continuous Trastuzumab Therapy in Breast Cancer Patients With Asymptomatic Left Ventricular Dysfunction.
abstract: BACKGROUND
  Adjuvant trastuzumab is a highly effective targeted treatment that improves survival for patients with HER2-positive breast cancer. However, trastuzumab interruption is recommended for patients who develop treatment-induced cardiotoxicity (i.e., decline in left ventricular ejection fraction [LVEF], with or without symptoms) and can lead to an incomplete course of treatment. We studied the cardiac safety of continuous trastuzumab therapy among patients with asymptomatic declines in LVEF.
  
  
  METHODS
  We retrospectively evaluated patients with HER2-positive breast cancer treated with adjuvant trastuzumab at our institution between 2005 and 2010. Treatment-induced cardiotoxicity was defined by an absolute decrease in LVEF of ≥10% to below 55% or an absolute decrease of ≥16%. Logistic regression was used to determine the association between candidate risk factors and treatment-induced cardiotoxicity.
  
  
  RESULTS
  Among 573 patients, 92 (16%) developed treatment-induced cardiotoxicity. Trastuzumab was continued without interruption in 31 of 92 patients with treatment-induced cardiotoxicity—all were asymptomatic with LVEF of ≥50% at cardiotoxicity diagnosis with median LVEF of 53% (range, 50%-63%), and none developed heart failure during follow-up. Risk factors associated with treatment-induced cardiotoxicity included age (p = .011), anthracycline chemotherapy (p = .002), and lower pretrastuzumab LVEF (p < .001).
  
  
  CONCLUSIONS
  Among patients who develop asymptomatic treatment-induced cardiotoxicity with LVEF of ≥50%, continuous trastuzumab therapy appears to be safe.
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA yua3@mskcc.org.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Yu
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Nandini U
authors.initials: NU
authors.lastname: Yadav
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Eaton
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Lung
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Howard T
authors.initials: HT
authors.lastname: Thaler
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Liu
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
authors.affiliation: Departments of Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Steingart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D066126:Cardiotoxicity; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Adjuvant chemotherapy; Breast cancer; Cardiotoxicity; Heart failure; Trastuzumab