Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction Journal Article


Authors: Hussain, Y.; Drill, E.; Dang, C. T.; Liu, J. E.; Steingart, R. M.; Yu, A. F.
Article Title: Cardiac outcomes of trastuzumab therapy in patients with HER2-positive breast cancer and reduced left ventricular ejection fraction
Abstract: Purpose: Asymptomatic decline in left ventricular ejection fraction (LVEF) or heart failure (HF) occurs in up to 25% of patients treated with trastuzumab and can result in incomplete breast cancer therapy. The cardiac safety of continuing trastuzumab in patients with asymptomatic LVEF decline is unknown. We report the cardiac outcomes of patients treated with trastuzumab after a significant asymptomatic LVEF decline. Methods: Patients with HER2-positive breast cancer and asymptomatic LVEF decline to < 50% during trastuzumab were identified from an institutional echocardiogram database. Patients who received trastuzumab with a LVEF < 50% were classified as the continued group, whereas patients who had trastuzumab held until LVEF improved to ≥ 50% or who had trastuzumab permanently discontinued were classified as the interrupted group. Cardiac events were defined as HF (New York Heart Association class III–IV) or cardiovascular death. Results: Sixty patients were included; the median age was 54 years. In 23 patients who continued trastuzumab, 14 (61%) tolerated trastuzumab without a cardiac event, 6 (26%) developed worsening LVEF (range 25–42%) leading to trastuzumab discontinuation, and three (13%) developed a cardiac event (1 HF, 2 possible/probable cardiovascular deaths). In 37 patients with interrupted trastuzumab, 15 (41%) were re-challenged with trastuzumab after LVEF improved to > 50%, 21 (57%) were not re-challenged, and one (3%) developed HF. More patients in the continued trastuzumab group had metastatic disease (39% vs. 5%, p = 0.002). The final LVEF after median follow-up of 633 days was similar between patients with trastuzumab continuation versus interruption (54% vs. 56%, p = 0.29). Conclusion: Continuation of trastuzumab after an asymptomatic LVEF decline to < 50% in patients who are expected to benefit from additional anti-HER2 therapy is a promising approach that warrants further investigation. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: adult; controlled study; major clinical study; drug tolerability; drug safety; drug withdrawal; follow up; breast cancer; heart disease; epidermal growth factor receptor 2; retrospective study; heart death; heart failure; cardiotoxicity; echocardiography; trastuzumab; heart left ventricle ejection fraction; cardiomyopathy; asymptomatic disease; human epidermal growth factor receptor 2 positive breast cancer; human; female; priority journal; article; cardio-oncology; new york heart association class
Journal Title: Breast Cancer Research and Treatment
Volume: 175
Issue: 1
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2019-05-01
Start Page: 239
End Page: 246
Language: English
DOI: 10.1007/s10549-019-05139-6
PUBMED: 30721443
PROVIDER: scopus
PMCID: PMC6494676
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Jennifer Liu
    118 Liu
  2. Chau Dang
    271 Dang
  3. Richard M Steingart
    174 Steingart
  4. Esther Naomi Drill
    93 Drill
  5. Anthony Yu
    90 Yu