Cancer therapy-related cardiac dysfunction (CTRCD) after radiation therapy for breast cancer: Results of the French BACCARAT study

Introduction

Radiation therapy (RT) for breast cancer (BC) can result in a broad spectrum of cardiotoxicity including subtle cardiac dysfunction that can occur early after treatment. In 2022, the first European Society of Cardiology (ESC) guidelines in cardio-oncology defined asymptomatic cancer therapy-related cardiac dysfunction (CTRCD). This newly defined event has never been studied in BC patients treated with RT.

Objective

To evaluate early to mid-term asymptomatic CTRCD occurrence and to analyze the association with radiation-induced cardiac exposure.

Method

The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40–75 years. Conventional and 2D Speckle tracking echocardiography was performed before, 6 and 24 months after RT. The present analysis included all patients with left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS) measurements available for the three-time points. Asymptomatic CTRCD, as defined in the latest ESC guidelines, combines information on LVEF and GLS decrease from baseline occurring 6 or 24 months after RT. Whole heart, left ventricle (LV), and coronary arteries dose-volume parameters were considered to evaluate the impact of cardiac exposure on CTRCD.

Results

The study included 72 BC (of 59 left-sided BC) patients with a mean age of 58 ± 8.2 years. A total of 32 (44%) patients developed any grade CTRCD during follow-up: 22 (31%) developed early dysfunction, and 14 (19%) developed midterm dysfunction with or without previous early dysfunction only in left BC patients. The cardiac doses were generally higher among patients with CTRCD rather than non-CTRCD. Significant dose-response relationships were observed between the risk of CTRCD and cardiac exposure, in particular LV exposure (OR for V2 LV dose = 1.03 (1.00–1.06) P = 0.01 and circumflex CX artery's mean dose OR = 2.44 (1.26–4.74) P = 0.008, D2 OR = 1.79 (1.13–2.85) P = 0.01 and V2 OR = 1.02 (1.01–1.04) P = 0.01. The results for the CX artery exposure were robust and significant after adjustment for classic cardiac risk factors (CVRF) and analyses according to the CTRCD grade; however, it did not remain significant for LV.

Conclusion

Our study suggests an association between specific cardiac structures and CTRCD 2 years after BC RT. considering CVRF. However, given the limited number of patients, further research is needed to understand the early mechanisms of radiation-induced CTRCD.