Tamoxifen: New mechanism for increased risk of uterine cancer discovered

by | Aug 25, 2025 | Health, Research

An international research team led by Professor Kirsten Kübler from the Berlin Institute of Health (BIH) has uncovered a previously unknown mechanism that explains why the breast cancer drug tamoxifen can increase the risk of secondary tumors in the uterus. The study, published in Nature Genetics, shows that tamoxifen directly activates the tumor-promoting PI3K signaling pathway and thus provides new insights into the development of therapy-related tumors.

Symbolic image (Credits: pixabay)
Symbolic image (Credits: pixabay)

Since the 1970s, tamoxifen has significantly improved the chances of survival of patients with estrogen receptor-positive breast cancer. Despite its effectiveness, the drug is known to increase the risk of uterine cancer in rare cases. The molecular causes of this side effect were previously unclear. The new study shows that in tamoxifen-associated uterine carcinomas, mutations in the Tumorgen PIK3CA, which often activate the PI3K signaling pathway in spontaneous uterine tumors, occur significantly less frequently. Instead, tamoxifen itself directly activates this signaling pathway, eliminating the need for genetic mutations.

The findings expand the understanding of how a successful cancer drug can paradoxically promote tumors in other tissues. Although the risk of uterine cancer remains low with tamoxifen and the benefits outweigh the risks, the results offer approaches for safer therapies. The team plans to investigate similar mechanisms in other drugs to develop personalized prevention and intervention strategies.

Original Paper:

Tamoxifen induces PI3K activation in uterine cancer | Nature Genetics

Editor: X-Press Journalistenbüro GbR

Gender Notice. The personal designations used in this text always refer equally to female, male and diverse persons. Double/triple naming and gendered designations are used for better readability. ected.

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