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Risk of heart failure after systemic treatment for early breast cancer: results of a cohort study



Anthracyclines and trastuzumab can increase the risk of heart failure (HF), but long-term cardiotoxicity data in breast cancer (BC) patients treated at younger ages are limited. Furthermore, it is unknown whether aromatase inhibitors are associated with HF risk.


HF risk was studied in a multicenter cohort of BC survivors treated during 2000–2009, at age < 61 years. Information on treatment and cardiovascular disease incidence was collected through medical records, general practitioners and cardiologists. Analyses included multivariable Cox regression and cumulative incidence curves.


In total, 10,209 women with a median age at BC diagnosis of 50.3 years and a median follow-up of 8.9 years were enrolled in the study. Anthracycline-based chemotherapy was associated with HF (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.41–3.39) and risk increased with increasing cumulative anthracycline dose. For trastuzumab, HF risk was highest within the first 2 years after treatment (HR0–2 years: 13.06, 95% CI 5.70–29.92) and decreased thereafter (HR2–4 years: 4.84, 95% CI 1.99–11.75 and HR≥4 years: 0.64, 95% CI 0.23–1.81). The 10-year cumulative incidence of HF was 4.8% (95% CI 3.2–6.8) among patients treated with anthracyclines and trastuzumab. One-third of patients who developed HF after trastuzumab had long-term impaired cardiac function. Patients treated with aromatase inhibitors alone also had higher HF risk (HR 2.18, 95% CI 1.24–3.82) compared to patients not receiving endocrine therapy.


Our results stress the importance of considering anthracycline-free regimens in BC patients who need trastuzumab-containing treatment. The association between aromatase inhibitors and HF needs confirmation.

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This study was funded by Pink Ribbon/the Dutch Cancer Society (Grant Number 2012.WO39.C143/NKI 2016-8192).

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Correspondence to Flora E. van Leeuwen.

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Jacobse, J.N., Schaapveld, M., Boekel, N.B. et al. Risk of heart failure after systemic treatment for early breast cancer: results of a cohort study. Breast Cancer Res Treat 185, 205–214 (2021).

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  • Breast cancer
  • Heart failure
  • Anthracyclines
  • Trastuzumab
  • Survivorship
  • Epidemiology