Tamoxifen-Induced Liver Injury in Patients With Breast Cancer: Frequency, Risk Factors and Clinical Course
Ayako Ueno1, Masayuki Ueno2,3, Mayo Nishikawa1
1Department of General Surgery, Kurashiki Central Hospital, Kurashiki, Japan.
Aim:
Tamoxifen is a widely used endocrine treatment for breast cancer, also responsible for drug-induced steatotic liver diseases. This study aimed to investigate the frequency, clinical course and risk factors for tamoxifen-induced liver injury in patients with breast cancer.
Methods:
We conducted a retrospective analysis of 192 patients with breast cancer who initiated tamoxifen therapy between January 2008 and December 2017, undergoing blood tests and abdominal ultrasonography after receiving tamoxifen for at least 1 year. Liver injury was defined as alanine transaminase and/or alkaline phosphatase levels exceeding twice the upper limit of the normal range. We explored the risk factors for CTCAE grade ≥ 2 tamoxifen-induced liver injury and validated the results with a cohort of additional 166 patients.
Results:
Among the 192 patients, 30 (15.6%) experienced tamoxifen-induced liver injury, including 13 patients with grade ≥ 2 liver injury. Although most patients with grade 1 liver injury experienced spontaneous resolution, several patients with grade ≥ 2 liver injury required treatment interruption/discontinuation or developed persistent liver injury. Progression to cirrhosis was suspected in two (1.0%) patients. High body mass index (BMI), diabetes, dyslipidemia and pre-existing liver steatosis were significantly associated with an increased risk of grade ≥ 2 liver injury.
Conclusions:
Tamoxifen-induced liver injury was observed in 15.6% of the patients. Metabolic factors, such as high BMI, diabetes, dyslipidemia and pre-existing liver steatosis, were considered potential predictors of CTCAE grade ≥ 2 liver injury. Collaboration with gastroenterologists should be encouraged in patients with grade ≥ 2 liver injuries, where spontaneous remission is uncommon.
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