Tamoxifen-Induced Hepatic Steatosis in Breast Cancer Patients

Tamoxifen, a selective oestrogen receptor modulator widely prescribed for hormone receptor–positive breast cancer, is associated with the development of hepatic steatosis in a substantial proportion of patients. Clinical series have reported new-onset fatty liver in approximately one-third to one-half of long-term users, frequently without overt symptoms but detectable on imaging. Mechanistic studies indicate that tamoxifen perturbs lipid homeostasis in hepatocytes by enhancing de novo lipogenesis. Central to this effect is the activation of sterol regulatory element-binding protein-1c and downstream enzymes such as fatty acid synthase and acetyl-CoA carboxylase, together with altered phosphorylation states that favour lipid synthesis over oxidation. Emerging work has also implicated mitogen-activated protein kinase pathways in this drug-induced metabolic shift. Clinically, tamoxifen-related steatosis does not appear to worsen cancer-specific survival but may aggravate insulin resistance and cardiovascular risk, underscoring the need for regular hepatic monitoring and metabolic risk management during adjuvant endocrine therapy.

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Tamoxifen-Induced Hepatic Steatosis in Breast Cancer Patients publication trend

The graph below shows the total number of articles in tamoxifen-induced hepatic steatosis in breast cancer patients across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatic steatosis: the accumulation of triglyceride-rich lipid droplets within hepatocytes, commonly referred to as fatty liver.

Selective oestrogen receptor modulator (SERM): a compound that acts as an oestrogen receptor agonist or antagonist depending on the tissue context.

De novo lipogenesis: the metabolic pathway by which acetyl-CoA is converted to fatty acids, primarily in the liver.

SREBP-1c: sterol regulatory element-binding protein-1c, a transcription factor that upregulates enzymes of fatty acid and triglyceride synthesis.

Acetyl-CoA carboxylase: the rate-limiting enzyme in fatty acid synthesis that converts acetyl-CoA to malonyl-CoA.

References

1. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology (2010).
2. The Effect and Mechanism of Tamoxifen-Induced Hepatocyte Steatosis in Vitro. International Journal of Molecular Sciences (2014).
3. Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer. PLOS ONE (2020).
4. Effects of Tamoxifen vs. Toremifene on fatty liver development and lipid profiles in breast Cancer. BMC Cancer (2021).
5. Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway. Clinical and Translational Medicine (2020).
6. Selective Estrogen Receptor Modulator-Associated Nonalcoholic Fatty Liver Disease Improved Survival in Patients With Breast Cancer. Medicine (2015).