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

• Published in: Breast cancer research and treatment 2021-07, Vol.188 (1), p.149-163
• Main Authors: Battisti, Nicolò Matteo Luca, Andres, Maria Sol, Lee, Karla A., Ramalingam, Sivatharshini, Nash, Tamsin, Mappouridou, Stephanie, Senthivel, Nishanthi, Asavisanu, Kalaprapa, Obeid, Mariam, Tripodaki, Elli-Sophia, Angelis, Vasileios, Fleming, Emily, Goode, Emily F., John, Susan, Rosen, Stuart D., Allen, Mark, Stanway, Susannah, Lyon, Alexander R., Ring, Alistair
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anthracycline; Breast cancer; Breast Neoplasms - drug therapy; Cancer research; Cardiotoxicity; Cardiovascular diseases; Clinical Trial; Clinical trials; Congestive heart failure; Demography; ErbB-2 protein; Female; Heart failure; Heart Failure - chemically induced; Humans; Incidence; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Oncology; Receptor, ErbB-2; Retrospective Studies; Risk Assessment; Stroke Volume; Targeted cancer therapy; Trastuzumab; Trastuzumab - adverse effects; Trastuzumab - therapeutic use; Ventricle; Ventricular Function, Left; Young Adult
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06192-w

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.