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

Purpose: 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. Methods: 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. Results: 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 (HR_0–2 years: 13.06, 95% CI 5.70–29.92) and decreased thereafter (HR_2–4 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. Conclusions: 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.