Heart failure after treatment for breast cancer

Abstract

Background: We aimed to develop dose-response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies.

Methods and results: A case-control study was performed within a cohort of breast cancer survivors treated during 1980-2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9-13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) -2 to 10]. In patients treated with anthracyclines, exposure of ≥20% of the heart to ≥20 Gy was associated with a rate ratio of 5.7 (95% CI 1.7-21.7) compared to <10% exposed to ≥20 Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247 mg/m² (IQR 240-319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m² , 95% CI 0.5-4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1-110.1) compared to no chemotherapy.

Conclusions: In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies.

Keywords: Anthracycline; Breast cancer; Heart failure; Radiation dose-response; Trastuzumab.

Figure 1

Excess rate ratio (ERR) in heart failure by cumulative anthracycline dose. The regression line is the best fitting linear dose–response relationship. This results in an ERR of 1.5% per mg/m² [95% confidence interval (CI) 0.5–4.1]. Squares indicate point estimates for dose categories (no anthracycline‐based chemotherapy, ≤240 mg/m² cumulative anthracycline dose, and >240 mg/m² cumulative anthracycline dose, see Table 2) and are plotted at the mean cumulative anthracycline dose of each category. There was no significant departure from linearity observed. Patients treated with trastuzumab were excluded from this analysis.