title: Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience.
abstract: OBJECTIVE
  To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX).
  
  
  METHODS
  Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF).
  
  
  RESULTS
  The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up.
  
  
  CONCLUSIONS
  The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Guarneri
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lenihan
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Durand
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Laura Boehnke
authors.initials: LB
authors.lastname: Michaud
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004699:Endocardium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008854:Microscopy, Electron; D008875:Middle Aged; D016017:Odds Ratio; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D018570:Risk Assessment; D013318:Stroke Volume / Q000187:drug effects; D013781:Texas; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab