Tamoxifen & Uterine Cancer โขRisk: A Potential Preventative Strategy
A new study offers promising insightsโ into a known side effect of a common breast cancer โtreatmentโฃ -โค the increased risk of uterine cancer. While โฃtamoxifen remains a highly effective therapy, research โขreveals how โ it can contribute to uterine โcancer advancement adn suggests a potential way โto mitigate this risk.
Researchers atโ Mass General Brigham, the Broad Institute, โDana-farber Cancer Institute, โคandโข the Berlin Institute of โฃHealth โ(BIH) discovered that tamoxifen activates a cell โgrowthโ signaling pathway in the uterus, specifically the PI3K-AKT pathway. This activation appearsโ to occurโ without causing the โฃtypical genetic mutations (specifically in the PIK3CA gene) often seen in uterineโ cancers that โdevelop independently of tamoxifen โคtreatment. โฃ Actually, uterine cancers linked to tamoxifen use โคshowed significantly lower rates of โtheseโค PIK3CA mutations.
the โฃstudy, published in Nature Genetics, demonstrated inโ miceโค thatโ tamoxifen exposure โled to increased activity in the PI3K-AKT pathway, driven in part by the growth-promoting hormone โIGF1. Crucially, when miceโข were treated with both tamoxifen and alpelisib – โฃaโฃ drug that blocks the PI3K pathway โค- PI3K-AKT signaling, IGF1 receptorโ activation, โขand cell proliferation were significantly reduced.
These โfindings โคsuggest that blocking theโฃ PI3K pathway โคcould offer aโ preventative measure against tamoxifen-associated uterine cancer.
“Futureโ clinical research can confirm whether combiningโ non-mutant selective PI3K inhibitors with tamoxifenโฃ reducesโค the risk of โฃuterine cancer andโข ultimately โsavesโ lives,” โsays Dr. โขRinath Jeselsohn of Dana-Farber Cancer Institute and the โขBroad Institute.โค this research could ultimatelyโฃ change how some breastโค cancers are treated, improving long-term outcomes for patients.
Source: Kรผbler, K.,et al. (2025). Tamoxifen โฃinduces PI3K activationโ in uterine cancer. Nature Genetics. doi.org/10.1038/s41588-025-02308-w
