Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer Journal Article

Authors: Yu, A. F.; Yadav, N. U.; Lung, B. Y.; Eaton, A. A.; Thaler, H. T.; Hudis, C. A.; Dang, C. T.; Steingart, R. M.
Article Title: Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer
Abstract: Trastuzumab improves outcomes among patients with HER2-positive breast cancer but is associated with a risk of treatment-induced cardiotoxicity (TIC). It is unclear how frequently TIC leads to trastuzumab interruption outside of prospective trials, and how TIC is managed in clinical practice. Patients with HER2-postive breast cancer receiving adjuvant trastuzumab from 2005 to 2010 were identified (n = 608). We evaluated the incidence, risk factors, and management of trastuzumab interruption due to TIC. In total, 488 (80 %) patients were treated with anthracycline prior to trastuzumab. Trastuzumab was interrupted in 108 (18 %) patients. Cumulative trastuzumab dose was lower in the interrupted group (median 86 vs. 108 mg/kg, p < 0.0001). The most common reason for interruption was TIC (66 of 108 patients): 20 had symptomatic heart failure and 46 had asymptomatic left ventricular ejection fraction (LVEF) decline. Patients with trastuzumab interruption for TIC were older (54 vs. 50 years, p = 0.014) with lower LVEF before anthracycline (63 vs. 67 %, p < 0.0001) and trastuzumab (62 vs. 67 %, p < 0.0001) therapy. Mean LVEF at baseline, TIC diagnosis, and follow-up after trastuzumab interruption was 63, 45, and 55 %, respectively. Thirty-three of 66 patients with TIC were re-challenged with trastuzumab, and five patients had recurrent LVEF decline. In clinical practice, trastuzumab interruption is common and most often due to TIC, with most patients receiving anthracycline prior to trastuzumab. Cardiac dysfunction improves after trastuzumab interruption but may not fully recover to baseline. Strategies to minimize cardiotoxicity and treatment interruption should be investigated to prevent persistent left ventricular dysfunction in affected patients.
Keywords: paclitaxel; adjuvant therapy; breast cancer; adjuvant chemotherapy; cardiotoxicity; trastuzumab; heart; therapy; follow-up; failure; trial comparing doxorubicin; cardiac dysfunction; nsabp b-31; events; troponin-i; rationale
Journal Title: Breast Cancer Research and Treatment
Volume: 149
Issue: 2
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2015-01-01
Start Page: 489
End Page: 495
Language: English
ACCESSION: WOS:000348976600017
DOI: 10.1007/s10549-014-3253-7
PUBMED: 25552363
PMCID: PMC4970316
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Clifford Hudis
    891 Hudis
  2. Chau Dang
    201 Dang
  3. Richard M Steingart
    132 Steingart
  4. Anne Austin Eaton
    122 Eaton
  5. Howard T Thaler
    227 Thaler
  6. Nandini Umesh Yadav
    9 Yadav
  7. Anthony Yu
    50 Yu
  8. Betty Ying-Feng Lung
    6 Lung