Early subclinical cardiovascular changes after radiotherapy detected by echocardiography in women with breast cancer: contribution of the MEDIRAD EARLY-HEART cohort

Overview & Synopsis

Background: Breast cancer (BC) represents a major public health burden worldwide. Significant advances in treatments have been made in recent decades. Among them, radiotherapy (RT) allows reducing local recurrence and deaths resulting from BC. However, RT for BC can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular adverse events (MACE). Consequently, to detect early subclinical cardiac alterations is of primary importance. Objective: One of the aims of the MEDIRAD EARLY-HEART study is to determine the short-term impact of BC RT on subclinical cardiac function by means of echocardiography and to explore the dose-response relationship. Methods: Launched in 2017, the ongoing EARLY-HEART study is a prospective multicenter cohort study including women with BC aged 40 to 75 years and treated by RT in the Netherlands, Germany, France, Portugal and Spain. All women were chemotherapy naive. Echocardiographic exams after the RT+6-month follow-up (FU) will be available in September 2021 to determine if significant subclinical cardiac function alterations occurred. A RT+24-month FU is currently ongoing to determine if eventual previous alterations persist. Myocardial deformation analysis was provided by the 2D-speckle-tracking echocardiography. The global longitudinal strain (GLS), its worsening > 10% and the global longitudinal strain rate (GLSR) will be considered to evaluate subclinical cardiac dysfunction. Results: The EARLY-HEART cohort included 258 women with BC, with a mean age of 58.2±8.1 years, 63.5% with left-sided BC. Presence of pre-existing cardiovascular (CV) risk factors were recorded to allow adjustments in further analyses: obesity was present in 21.0% of the sample (mean body mass index of 26.3±4.6 kg/m²), hypertension in 48.2%, diabetes in 5.4% and 47.8% were current or former smoker. RT total dose varied from 40.05 Gray (Gy) to 50.40 Gy, and 46.1% received a boost (mean boost dose of 11.9±1.9 Gy). Among the 258 patients, 63.9% received concomitant hormonotherapy. Regarding subclinical cardiac investigations at baseline (before RT), 242 patients (93.8%) performed echocardiography exams, yielding a mean GLS of -19.3±3.3%. Full echocardiography analyses after the 6-month FU will be available soon to explore potential alterations of myocardial function between pre-RT time-point, 6-month and 24-month post-RT time-points using paired t tests. Future EARLY-HEART analyses will also provide accurate absorbed dose of cardiac structures (whole heart, right and left ventricles, right and left atrium) based on 3D-dosimetry to explore dose-response relationships using multivariate regressions. Subgroup and sensitivity analyses will be performed. Results of analyses of the relationship between radiation dose and subclinical cardiac function will be presented. Conclusion: Using strain analysis from echocardiography, the impact of RT on subclinical cardiac function in patients with BC are being explored within the MEDIRAD EARLY-HEART project. Epidemiological data regarding early alteration of GLS could contribute to adaptions in clinical practice about CV monitoring.