BACKGROUND: Early identification of cardiotoxicity of chemotherapy is crucial. Gene expression is considered a promising tool. AIM: To validate the new speckle tracking values, high-sensitive (Hs) troponin and expression of TNNI3K and RyR2 genes for early detection of cardiotoxicity. METHODS: Fifty patients with cancer breast on Anthracycline chemotherapy were subjected to speckle tracking echocardiography and Hs troponin measurement. Relative expression of TNNI3K and RyR2 genes were determined by RT-PCR. RESULTS: Fifty female patients with age (43.89 ± 6.4) were included. Fourteen patients (28%) developed cardiotoxicity, diagnosed by decrease GLS >
15%. Compared to GLS, Hs-Troponin has sensitivity 73%, specificity 100%, PPV 78.5% and NPV 100%. Cutoff point of GLS >
10% had sensitivity 95%, specificity 78%, PPV 81% and NPV 84%. Using a cutoff of 24% change in TNNI3K Expression
sensitivity 100%, specificity 74%, PPV 79.5% and NPV 100%. Using a cutoff of 25% in RYR-2 expression
sensitivity 67% and specificity 59% with less PPV and NPV (62% and 64%). Adding GLS change >
10% to Hs troponin and TNNI3K expression resulted in highest sensitivity (100%) and specificity (95.5%) with 96% PPV and 100% NPV. CONCLUSION: Cutoff point of GLS >
10%, Hs-Troponin and TNNI3K gene expression are reliable test for early detection of cardiotoxicity. TRIAL REGISTRATION NUMBER (IRB): 042024100222.