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. 2021 Jul;188(1):149-163.
doi: 10.1007/s10549-021-06192-w. Epub 2021 Apr 5.

Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

Nicolò Matteo Luca Battisti  1 , Maria Sol Andres  2 , Karla A Lee  1 , Sivatharshini Ramalingam  2 , Tamsin Nash  1 , Stephanie Mappouridou  1 , Nishanthi Senthivel  1 , Kalaprapa Asavisanu  1 , Mariam Obeid  1 , Elli-Sophia Tripodaki  1 , Vasileios Angelis  1 , Emily Fleming  1 , Emily F Goode  1 , Susan John  1 , Stuart D Rosen  2 , Mark Allen  1 , Susannah Stanway  1 , Alexander R Lyon  2 , Alistair Ring  3
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Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

Nicolò Matteo Luca Battisti et al. Breast Cancer Res Treat. 2021 Jul.

Abstract

Purpose: Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates [left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation] and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.

Methods: Patients receiving curative trastuzumab between 2011 and 2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher's exact test, Chi-squared and logistic regression were used.

Results: 931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%). Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline ≥ 10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed. Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p = 0.002).

Conclusions: Cardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity.

Keywords: Breast cancer; Cardiotoxicity; Early stage; Trastuzumab.

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