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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

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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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

The statistical analysis code generated during the current study is available from the corresponding author on reasonable request.

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Acknowledgements

The authors wish to acknowledge the support of the Royal Marsden NIHR Biomedical Research Centre for Cancer and The Cridlan Ross Smith Charitable Trust. ARL is supported by the Leducq Transatlantic Cardio-Oncology Network.

Funding

Dr. Battisti is supported by a fellowship of The Cridlan Ross Smith Charitable Trust. Dr. Battisti and Dr. Ring wish to acknowledge the support of The Royal Marsden NIHR Biomedical Research Centre for Cancer. Dr. Tripodaki is funded by a scholarship from the Hellenic Society of Clinical Oncology (HESMO). The remaining authors have no funding to report.

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Authors and Affiliations

  1. Breast Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, Surrey, UK

    Nicolò Matteo Luca Battisti, Karla A. Lee, Tamsin Nash, Stephanie Mappouridou, Nishanthi Senthivel, Kalaprapa Asavisanu, Mariam Obeid, Elli-Sophia Tripodaki, Vasileios Angelis, Emily Fleming, Emily F. Goode, Susan John, Mark Allen, Susannah Stanway & Alistair Ring

  2. Cardio-Oncology Service, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, Chelsea, London, SW3 6NP, UK

    Maria Sol Andres, Sivatharshini Ramalingam, Stuart D. Rosen & Alexander R. Lyon

Authors
  1. Nicolò Matteo Luca Battisti
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Contributions

NMLB, MA, ARL and AR conceived and designed the analysis. NMLB, KAL, TN, SM, NS, KA, MO, EST, VA, EF, EFG, SJ collected the data. NMLB performed the analysis. NMLB, MSA, KAL, SR, TN, SM, NS, KA, MO, EST, VA, EF, EFG, SJ, SDR, MA, SS, ARL and AR wrote the paper.

Corresponding author

Correspondence to Alistair Ring.

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Conflict of interest

Dr. Battisti has received travel grants from Genomic Health and Pfizer and speaker fees from Pfizer and AbbVie. Dr. Lyon has received speaker, advisory board or consultancy fees and/or research grants from Pfizer, Novartis, Servier, Astra Zeneca, Bristol Myers Squibb, GSK, Amgen, Takeda, Roche, Janssens-Cilag Ltd, Clinigen Group, Eli Lily, Eisai Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health and Heartfelt Technologies Ltd. Dr. Ring has received advisory board and speaker fees from Roche, Novartis, Pfizer, MSD and Lilly. Dr. Andres, Dr. Lee, Dr Ramalingam, Dr. Nash, Dr Mappouridou, Dr. Senthivel, Dr. Asavisanu, Dr. Obeid, Dr. Tripodaki, Dr. Angelis, Dr. Fleming, Dr. Goode, Dr. John, Professor Rosen, Dr. Allen, Dr. Stanway have no conflicts of interest.

Ethical approval

This analysis was approved as a Service Evaluation by The Committee for Clinical Review of The Royal Marsden NHS Foundation Trust.

Informed consent

No individual person’s data are included in the manuscript in any form and therefore no consents for publication were required.

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Battisti, N.M.L., Andres, M.S., Lee, K.A. et al. 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. Breast Cancer Res Treat 188, 149–163 (2021). https://doi.org/10.1007/s10549-021-06192-w

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