Trastuzumab (TRZ) improves survival in women with HER-2-positive breast cancer but is associated with significant cardiotoxicity, especially when administered after anthracyclines (AC) and cyclophosphamide. Methods: We conducted an ambispective cohort study from an oncology center to evaluate the cardiac safety of trastuzumab combined with anthracyclines in women with stage I-III HER-2-positive breast cancer who received a regimen based on AC (doxorubicin and cyclophosphamide) followed by trastuzumab between January 2017 and December 2022. Cardiovascular risk factors such as left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and treatment discontinuation were collected. Cardiac events (CE) were defined according to the new European Society of Cardiology (ESC) 2022 criteria (including reduction in LVEF and GLS). In addition, Cox regression was used to predict associations with cardiotoxic development. Results: Of 205 women, median were 52 years old (IQR 42-59). Eighty-four presented with TRZ-induced cardiotoxicity, with a median treatment duration of 9 months (IQR 8-11) (LVEF reduction ≥ 10%) and 7 months (IQR 6-8) (GLS reduction ≥ 15%), respectively. Age older than 65 years (HR:1.67; 95% CI 0.98-2.8; P=0.05), history of coronary artery disease (HR:4.67; 95% CI 1.4-14; P=0.012), and adjuvant radiotherapy to the left breast (HR:1.34; 95% CI 0.8-2.2 P=0.242) were associated with the development of early cardiotoxicity. Conclusions: The incidence of cardiotoxicity in breast cancer patients treated with AC associated with TRZ is high given the new ESC criteria with the performance of GLS as a diagnostic test. These findings suggest more intensive cardiac monitoring in patients with risk factors over 65 years of age with previous coronary artery disease, and exposed to radiotherapy in the left breast.