title: Role of Troponins I and T and N-Terminal Prohormone of Brain Natriuretic Peptide in Monitoring Cardiac Safety of Patients With Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Trastuzumab: A Herceptin Adjuvant Study Cardiac Marker Substudy.
abstract: Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however, higher increases from baseline were seen in patients with TRCD compared with patients without.
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zardavas
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suter
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Jutta
authors.initials: J
authors.lastname: Steinseifer
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Noe
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lauer
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Nedal
authors.initials: N
authors.lastname: Al-Sakaff
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart-Gebhart
authors.affiliation: Dimitrios Zardavas, Breast International Group; Martine J. Piccart-Gebhart and Evandro de Azambuja, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Thomas M. Suter, Bern University Hospital, Bern; Jutta Steinseifer, Johannes Noe, Sabine Lauer, and Nedal Al-Sakaff, F. Hoffmann-La Roche, Basel, Switzerland; and Dirk J. Van Veldhuisen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D066126:Cardiotoxicity / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D019210:Troponin I; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); C508053:ERBB2 protein, human