December 2021: mdm2 gene amplification in luminal breast cancer

First objective of this study was the hypothesis-driven discovery of biomarkers involved in tumor progression upon xenotransplantation of luminal, i.e., estrogen receptor (ER)-positive breast cancer (BC) into humanized mice. The second objective was the marker validation and correlation with the clinical outcome of luminal breast cancer patients from the GeparTrio trial.

Highlights:
• An mdm2 gene amplification propels growth and progression of ER-positive breast cancer in a preclinical humanized tumor mouse (HTM) model, which replicates a functional human immune system
• mdm2 inhibition of ER-positive BC cells in vitro reduces cell proliferation and migration and induces tumor cell apoptosis.
• An unfavorable impact of an mdm2 gain on survival outcome of luminal BC patients is mainly caused within the luminal-A BC subcohort.
• Prospective studies are required to verify the suitability of mdm2 for advanced Luminal BC stratification and therapeutic targeting of ER-positive BC.

Conclusion: We provide evidence for an enhanced luminal BC stratification based on mdm2. Moreover, mdm2 can potentially be utilized as a therapeutic target in the luminal subtype.

Wege AK, Rom-Jurek EM, Jank P, et al. mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease. Int J Cancer. 2021; doi: 10.1002/ijc.33911.

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