Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy
Authors: Yamashita K , Tanaka H , Hatazawa K , Tanaka Y , Shono A , Suzuki M , Sumimoto K , Shibata N , Yokota S , Suto M , Dokuni K , Matsumoto K , Minami H , Hirata K 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity.

Purpose
Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer.

Methods
We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of &gt;10% to an absolute value of &lt;53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥ 240mg/m², (2) age ≥ 65-year-old, (3) body mass index ≥ 30kg/m², (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥ 100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker.

Results
The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p &lt; 0.001), lower global longitudinal strain (18.4 ± 2.8% vs. 20.0 ± 2.6%, p = 0.06) and higher E/e’ (10.4 (8.9-13.0) vs. 9.0 (7.4-10.9), p = 0.06) compared to those without.
Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²).

Conclusions
Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy.
Abstract Figure.