Long-term cardiopulmonary consequences of treatment-induced cardiotoxicity in survivors of ERBB2-positive breast cancer Journal Article


Authors: Yu, A. F.; Flynn, J. R.; Moskowitz, C. S.; Scott, J. M.; Oeffinger, K. C.; Dang, C. T.; Liu, J. E.; Jones, L. W.; Steingart, R. M.
Article Title: Long-term cardiopulmonary consequences of treatment-induced cardiotoxicity in survivors of ERBB2-positive breast cancer
Abstract: Importance: Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-induced cardiotoxicity, most commonly manifest by an asymptomatic decline in left ventricular ejection fraction (LVEF). Little is known to date regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in patients who survive trastuzumab-treated breast cancer. Objective: To determine whether treatment-induced cardiotoxicity recovers or is associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer. Design, Setting, and Participants: This cross-sectional case-control study enrolled patients with nonmetastatic ERBB2-positive breast cancer after completion of trastuzumab-based therapy (median, 7.0 [interquartile range (IQR), 6.2-8.7] years after therapy) who met 1 of 2 criteria: (1) cardiotoxicity (TOX group) developed during trastuzumab treatment (ie, asymptomatic decrease of LVEF≥10% from baseline to <55% [n = 22]) or (2) no evidence of cardiotoxicity during trastuzumab treatment (NOTOX group [n = 20]). Patients were treated at the Memorial Sloan Kettering Cancer Center. Fifteen healthy control participants (HC group) were also enrolled for comparison purposes. All groups were frequency matched by age strata (<55, 55-64, and ≥65 years). Data were collected from September 9, 2016, to August 10, 2018, and analyzed from November 20, 2018, to August 12, 2019. Main Outcomes and Measures: Speckle-tracking echocardiography and maximal cardiopulmonary exercise testing were performed to measure indices of left ventricular function (including LVEF and global longitudinal strain [GLS]) and peak oxygen consumption (peak VO2). Results: A total of 57 participants (median age, 60.8 [IQR, 52.7-65.7] years) were included in the analysis. Overall, 38 of 42 patients with breast cancer (90%) were treated with anthracyclines before trastuzumab. Resting mean (SD) LVEF was significantly lower in the TOX group (56.9% [5.2%]) compared with the NOTOX (62.4% [4.0%]) and HC (65.3% [2.9%]) groups; similar results were found for GLS (TOX group,-17.8% [2.2%]; NOTOX group,-19.8% [2.2%]; HC group,-21.3% [1.8%]) (P <.001). Mean peak VO2 in the TOX group (22.9 [4.4] mL/kg/min) was 15% lower compared with the NOTOX group (27.0 [5.3] mL/kg/min; P =.03) and 25% lower compared with the HC group (30.5 [3.4] mL/kg/min; P <.001). In patients with breast cancer, GLS was significantly associated with peak VO2 (β coefficient,-0.75; 95% CI,-1.32 to-0.18). Conclusions and Relevance: Treatment-induced cardiotoxicity appears to be associated with long-term marked impairment of cardiopulmonary function and may contribute to increased risk of late-occurring cardiovascular disease in survivors of ERBB2-positive breast cancer. © 2019 American Medical Association. All rights reserved.
Keywords: adult; cancer survival; controlled study; middle aged; major clinical study; case control study; drug efficacy; drug safety; outcome assessment; breast cancer; epidermal growth factor receptor 2; cardiotoxicity; cross-sectional study; trastuzumab; exercise test; chronic drug administration; heart left ventricle function; heart left ventricle contraction; human; priority journal; article; speckle tracking echocardiography; heart muscle oxygen consumption
Journal Title: JAMA Cardiology
Volume: 5
Issue: 3
ISSN: 2380-6583
Publisher: American Medical Association  
Date Published: 2020-03-01
Start Page: 309
End Page: 317
Language: English
DOI: 10.1001/jamacardio.2019.5586
PUBMED: 31939997
PROVIDER: scopus
PMCID: PMC6990842
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Jennifer Liu
    49 Liu
  2. Chau Dang
    195 Dang
  3. Richard M Steingart
    132 Steingart
  4. Chaya S. Moskowitz
    196 Moskowitz
  5. Anthony Yu
    50 Yu
  6. Lee Winston Jones
    129 Jones
  7. Jessica M Scott
    23 Scott
  8. Jessica Flynn
    39 Flynn