Researchers from Germany and the US have discovered how the breast cancer drug tamoxifen can increase the risk of tumours in the uterus, in a study using mice. 

Tamoxifen is a drug used to treat breast cancers that are responsive to the hormone oestrogen, and it has increased the survival rate of millions of patients. However, its administration has been associated with a rare side effect — an elevated risk of uterine cancer. 

By sequencing the genes in human uterine cancer, researchers from the Berlin Institute of Health at EARA member Charité and several collaborators in the US, discovered that uterine tissue from patients with cancer associated with tamoxifen therapy has fewer mutations than tissue from spontaneous uterine cancers in genes related to the protein PI3K, which acts as a trigger for cancer formation.  

By treating cancer-free mice with tamoxifen, the team discovered that tamoxifen directly turns on genes in the PI3K pathway in the uterus.  

“Tamoxifen bypasses the need for genetic mutations in the PI3K signaling pathway, one of the key drivers of uterine cancer, by directly providing the stimulus for tumor formation.”, said Kirsten Kübler, author of the study published in Nature Genetics. 

The overall risk of developing uterine cancer remains low and it is outweighed by the benefits of its use in treating breast cancer. Nevertheless, these findings can improve the safety of this drug and potentially others with similar mechanisms.