Comprehensive Evaluation of Hepatotoxicity Following Radiation Therapy in Breast Cancer Patients

<b>Purpose:</b> The liver is susceptible to adverse effects from radiation therapy (RT) and systemic therapy (ST) for breast cancer, given its anatomical proximity. Thus, we evaluated hepatotoxicity after RT and ST for breast cancer. <b>Methods:</b> This multicenter retrospective study included breast cancer patients treated with RT in 2021 and underwent a liver function test (LFT) before and after RT. Patients with bilateral breast cancer or a history of thoracic or abdominal RT and liver disease were excluded. Changes in Common Terminology Criteria for Adverse Events (CTCAE) grading of liver enzyme elevation (LEE) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and its associations with Dose-volume histogram (DVH) parameters and other clinical factors were analyzed. <b>Results:</b> In total, 529 patients were included in the analysis. Median values of mean liver dose, V5Gy, V10Gy, and V20Gy dose to the liver were 1.37 Gy, 4.3%, 2.1%, and 0.9%, respectively. In the post-RT LFT, 6 (1.1%), 9 (1.7%), and 25 (4.7%) patients showed CTCAE grade elevation of AST, ALT and ALP, respectively, with most cases being grade 1. Three patients (0.6%) met the diagnostic criteria for radiation-induced liver disease (RILD). In multivariate logistic regressions including various DVH parameters, neoadjuvant therapy was associated with LEE. <b>Conclusions:</b> The incidences of LEE and RILD after multimodal therapy for breast cancer were limited, suggesting that RT and ST can be considered safe in terms of hepatotoxicity. Nevertheless, caution in treating patients who underwent neoadjuvant therapy, especially to those with underlying liver disease, might help minimize LEE.