title: Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy.
abstract: OBJECTIVE
  Recent studies in breast cancer patients and Trastuzumab therapy (Herceptin) showed a development of a toxic cardiomyopathy as a severe complication. The aim of this study was to discover early changes in cardiac function and morphology.
  
  
  METHODS
  We studied 42 female patients with Her-2/-neu over-expression in breast cancer by echocardiography before, 3, and 6 months after start of the adjuvant Herceptin therapy. All values were mean value ± standard deviation.
  
  
  RESULTS
  After 3 or 6 months of a trastuzumab therapy we discovered significant increases in the diastolic and systolic left ventricle volume indices (LV-DVI 32.4 ± 8.5 vs. 38.5 ± 8.7 vs. 40.3 ± 10.3 ml/m², p < 0.001 and LV-SVI 12.6 ± 4.0 vs. 15.7 ± 4.7 vs. 17.2 ± 6.8 ml/m², p < 0.001), an increase of the end-diastolic and end-systolic LV diameter (LVEDD 46.8 ± 4.2 vs. 48.0 ± 4.7 vs. 49.7 ± 4.5 ml/m², p < 0.01; LVESD 28.3 ± 4.2 vs. 31.0 ± 4.7 vs. 32.3 ± 4.9 mm, p < 0.001), a reduced systolic ventricle function determined by the tissue Doppler imaging (TDI) velocity (9.2 ± 2.5 vs. 8.0 ± 1,7 vs. 7.7 ± 1.5 cm/s, p < 0.001), fractional shortening (39,6 ± 7.5 vs. 35.4 ± 7.4 vs. 35.2 ± 7.0%, p < 0.01), and the LV-EF Simpson biplane [62.0 ± 5.1 vs. 60.1 ± 6.3 (p = ns) vs. 58.4 ± 7.9%, p < 0.01] compared to pretreatment values. There was also an increase of the left atrial volume index (21.4 ± 6.2 vs. 26.2 ± 7.9 vs. 29.7 ± 8.8 ml/m², p < 0.001), a decrease of the median TDI atrial velocities (11.9 ± 2.4 vs. 10.5 ± 2.8 vs. 10.1 ± 2.1 cm/s, p < 0.01), an increase of the peak early diastolic filling velocities (73.1 ± 15.4 vs. 83.1 ± 16.4 vs. 82.2 ± 19.4 cm/s, p < 0.05), and an increase of the median mitral valve insufficiency degree (0.64 ± 0.65 vs. 1.03 ± 0.76 vs. 1.11 ± 0.73°, p < 0.001). We could not detect a significant increase in diastolic dysfunction. Also right heart diameters and function did not change significantly. Most patients stayed in an asymptomatic stage of cardiac disease.
  
  
  CONCLUSIONS
  The blockade of Her2/-neu receptors with trastuzumab in patients with breast cancer led to measurable alterations of left ventricular volume, left atrial volume, and systolic function as early as 3 months after start of treatment.
authors.affiliation: Medizinische Klinik I, Kardiologie und Angiologie, Klinikum Worms, Akademisches Lehrkrankenhaus der Johannes-Gutenberg-Universität, Mainz, Germany. StefanAndreas.Lange@googlemail.com
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Lange
authors.forename: Bernd
authors.initials: B
authors.lastname: Ebner
authors.forename: Astrid
authors.initials: A
authors.lastname: Wess
authors.forename: Matthias
authors.initials: M
authors.lastname: Kögel
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Thomas
authors.initials: T
authors.lastname: Hitschold
authors.forename: Jens
authors.initials: J
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016279:Atrial Function, Left / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab