Herceptin (trastuzumab) mediated cardiotoxicity

Herceptin-Mediated Cardiotoxicity

Herceptin (trastuzumab) is a recombinant, humanised, monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of HER2-positive breast and gastric cancers.

Herceptin carries a risk of cardiotoxicity, manifesting as left ventricular (LV) systolic dysfunction, conventionally assessed for by transthoracic echocardiography (1).

A small study in patients who had undergone treatment with trastuzumab +/- anthracycline >=5 years previously (n=40) found 25% had LVEF (left ventricular ejection fraction) <50%, 30% had N-terminal pro-B-type natriuretic peptide >125 pg/mL, 8% had high-sensitivity cardiac troponin T >14 ng/L and 33% had new hypertension (2):

• researchers note that to the best of their knowledge, their study is the first to assess cardiotoxicity greater than 5 years post-trastuzumab and anthracycline therapy using a comprehensive CMR protocol, cardiac biomarkers and cardiovascular risk factor assessment
• the majority of participants received both trastuzumab and anthracycline therapy; they are unable to comment on the effects of trastuzumab alone
• all of the participants in this study had normal left ventricular ejection fraction prior to treatment
• study results:
  • median time since completion of trastuzumab was 7.8 years (range 5.9–10.8 years) and 90% received prior anthracycline
  • 25% of participants had LVSD (left ventricular systolic dysfunction)
  • 30% of participants had N-terminal pro-B-type natriuretic peptide >125 pg/mL and 8% had high-sensitivity cardiac troponin T >14 ng/L
  • 33% of participants had a new finding of hypertension
  • 58% had total cholesterol >5.0 mmol/L, 43% had triglycerides >1.7 mmol/L and 5% had a new diagnosis of diabetes
• the study authors concluded:
  • the presence of asymptomatic LVSD, abnormal cardiac biomarkers and cardiac risk factors in participants treated with trastuzumab and anthracycline at least 5 years previously is common, even in those with normal LVEF on completion of treatment
  • the findings reinforce the relevance of comprehensive evaluation of cardiovascular risk factors following completion of cancer therapy, in addition to LVEF assessment

References:

1. Jiang J, Liu B, Hothi SS. Herceptin-Mediated Cardiotoxicity: Assessment by Cardiovascular Magnetic Resonance. Cardiol Res Pract. 2022 Feb 27;2022:1910841. doi: 10.1155/2022/1910841. PMID: 35265371; PMCID: PMC8898877.
2. Glen C, Morrow A, Roditi G, et al Cardiovascular sequelae of trastuzumab and anthracycline in long-term survivors of breast cancer. Heart Published Online First: 16 December 2023. doi: 10.1136/heartjnl-2023-323437.