Evaluation of molecular predictors of cardiotoxicity in breast cancer patients and multiparametric clinical, biohumoral, and echocardiographic monitoring using speckle tracking echocardiography

Background Antineoplastic drugs used in breast cancer (BC) treatment can cause cardiovascular complications, sometimes severe. Purpose The aim of our study was to conduct a multiparametric evaluation considering new molecular predictors of cardiotoxicity. In particular, we investigated the role of pathogenic variants of the BRCA gene, which is implicated in the pathogenesis of hereditary BC. Methods This is a multicenter, prospective, observational study conducted in various cardiology and oncology units in Sicily from February 2021 to February 2024. Asymptomatic women with newly diagnosed BC, candidates for anthracycline therapy, were enrolled. All patients underwent a comprehensive standard two-dimensional echocardiographic examination and assessment of myocardial deformation indices using speckle tracking echocardiography (STE). The standard chemotherapy regimen included Epirubicin + Cyclophosphamide, followed by Paclitaxel. Genetic testing for BRCA was performed on peripheral blood samples, with the identification of pathogenic variants (PVs) through Next Generation Sequencing (NGS). The study population was divided into two groups based on the presence of BRCA1 variants. Patients were assessed at baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3), and 24 months (T4). Results A total of 96 patients were consecutively enrolled, of whom 50 completed follow-up (mean age 48.6 ± 8.7 years). The most common histological subtype was invasive ductal carcinoma (72%). Genetic testing identified 13 patients with BRCA1 PVs. Significant reductions in standard 2D echocardiographic parameters (LV ejection fraction and TAPSE) were observed only at later stages, starting from T3. However, STE techniques proved to be more sensitive predictors of cardiotoxicity from the early months of follow-up (T1-T2). LV and RV GLS showed significant reductions, corresponding with increased levels of NT-proBNP and high-sensitivity troponin T. Based on BRCA1 variant status, we identified two subgroups: Subgroup A (BRCA-mutated) with 13 patients and Subgroup B (wild-type) with 37 patients. There were no significant differences between the two subgroups in terms of cardiovascular risk factors, HFA-ICOS score, or biohumoral parameters. However, STE parameters and LVEF showed significant variations only in the BRCA-mutated group. Among BRCA-mutated patients, 7 out of 13 developed mild cardiotoxicity at T3, and 1 patient developed severe cardiotoxicity. In the wild-type group, only 5 out of 37 patients developed mild cardiotoxicity, and none developed severe cardiotoxicity (p-value <0.05). Conclusions Our study confirmed that LV GLS is a sensitive predictor of cardiotoxicity, significantly decreasing during follow-up before alterations in LVEF become apparent. The presence of BRCA PVs could be used as an independent predictor of the risk of developing cardiotoxicity.