Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan

Wei-Ting Chang; Po-Wei Chen; Hui-Wen Lin; Sheng-Hsiang Lin; Yi-Heng Li

doi:10.1002/ehf2.13591

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan

ESC Heart Fail. 2021 Dec;8(6):5149-5158. doi: 10.1002/ehf2.13591. Epub 2021 Sep 4.

Authors

Wei-Ting Chang^{1

2

3}, Po-Wei Chen^{1

4}, Hui-Wen Lin^{4

5}, Sheng-Hsiang Lin^{1

5

6}, Yi-Heng Li⁴

Affiliations

¹ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
³ Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
⁴ Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁵ Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁶ Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Aims: In contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and most are free from traditional cardiovascular risk factors. Despite trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) being reported, its incidence and predictors remain unknown in Taiwan.

Methods and results: Through a three-hospital retrospective cohort study, we analysed the incidence of MACCE in 386 breast cancer patients' exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13 502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab non-users, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4 and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67 and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246-1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than non-users.

Conclusions: From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.

Keywords: Breast cancer; Cardiotoxicity; MACCE; Trastuzumab.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / complications
Breast Neoplasms* / drug therapy
Breast Neoplasms* / epidemiology
Cardiotoxicity* / epidemiology
Cardiotoxicity* / etiology
Female
Humans
Retrospective Studies
Taiwan / epidemiology
Trastuzumab / adverse effects

Substances

Trastuzumab