A pooled analysis of the cardiac events in the trastuzumab adjuvant trials

Evandro de Azambuja, Noam Ponde, Marion Procter, Priya Rastogi, Reena S. Cecchini, Matteo Lambertini, Karla Ballman, Alvaro Moreno Aspitia, Dimitrios Zardavas, Lise Roca, Richard D. Gelber, Martine Piccart-Gebhart, Thomas Suter

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Trastuzumab-associated cardiotoxicity remains an issue for patients with HER2-positive breast cancer. This pooled analysis of 3 adjuvant trials investigated the incidence, timing, impact on treatment completion, and risk factors for trastuzumab-associated cardiotoxicity. Methods: This is an individual patient data level pooled analysis of HERA, NSBAP B-31, and NCCTG 9831 (Alliance Trials). Definitions of cardiac events were as per each individual study. Results: A total of 7445 patients enrolled in the 3 trials were included in the analysis, of which 4017 were in the trastuzumab and 3428 in the control (observation) arms, respectively. Median follow-up exceeded 10 years (119.2–137.2 months). Nearly all patients (97.4%) in the trastuzumab arms received anthracycline-based chemotherapy. In total, 452 patients in the trastuzumab arms experienced a cardiac event (11.3%), with most being mildly symptomatic or asymptomatic left ventricular ejection fraction (LVEF) decrease (351 patients, 8.7%). Severe congestive heart failure was more common in the trastuzumab arm (2.3%) than in the control arm (0.8%). Most cardiac events occurred during trastuzumab treatment (78.1%) and cardiac events were the main cause of discontinuation across the sample (10.0%); nevertheless, a large majority of patients completed trastuzumab treatment (76.2%). Baseline risk factors that were significantly associated with the development of cardiac events were baseline LVEF < 60%, hypertension, body mass index > 25, age ≥ 60 and, non-Caucasian ethnicity. Conclusion: One year of trastuzumab increases the risk of cardiac events, though most consist of asymptomatic or mildly symptomatic LVEF drops. Adjuvant trastuzumab should be considered a safe treatment from a cardiac standpoint for most patients. Trastuzumab-associated cardiotoxicity is the main cause of discontinuation and further research is needed to individualize prevention and management.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number1
StatePublished - Jan 1 2020


  • Breast cancer
  • Cardiotoxicity
  • LVEF
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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