Trajectory and Determinants of Left Ventricular Dysfunction Following Anthracycline-Based Therapy Among Breast Cancer...

Background: Doxorubicin and trastuzumab are effective breast cancer therapies but carry cardiotoxicity risk, indicated by decreased left ventricular ejection fraction (LVEF). This study aimed to analyze LVEF decline trends, cardiotoxicity incidence, and associated risk factors in breast cancer patients receiving doxorubicin with or without trastuzumab at Dharmais National Cancer Center Hospital, Jakarta. Methods: A retrospective cohort study was conducted using medical records of female patients aged ≥18 years with serial echocardiography (baseline and ≥1 follow-up) and ≥3 years of follow-up. Cardiotoxicity was defined as an absolute LVEF decline of ≥10% from baseline to <53%. We used the Mann-Whitney U test for LVEF trends, the Chi-square or Fisher's exact for risk factor associations, and Firth's Cox proportional hazards model for relative risk estimation. Results: Among the 301 patients, LVEF declined significantly at the fourth and sixth chemotherapy cycles and remained reduced during follow-up beyond 3 years. Cardiotoxicity occurred in 20 patients (6.65%), while 72 patients (23.92%) had borderline low LVEF. Significant risk factors for cardiotoxicity were continued trastuzumab-based chemotherapy (_adjHR 3.79; 95% CI 1.39-9.23) and a history of hypertension (_adjHR 0.2; 95% CI 0.02-0.81). This apparent protective effect of hypertension is likely due to the concurrent use of cardioprotective anti-hypertensive medications in this subgroup. Conclusions: Intensive cardiac monitoring is essential for breast cancer patients receiving sequential trastuzumab therapy, especially those with cardiovascular risk factors. Additional study with extended monitoring, more sensitive cardiac parameters, and detailed evaluation of concurrent cardioprotective therapies are warranted.