The genomic landscape of breast cancer brain metastases: a...

The genomic landscape of breast cancer brain metastases: a systematic review
The Lancet Oncology - December 2020.
"This systematic review provides a detailed overview of the most commonly mutated genes identified in samples of breast cancer brain metastases and their clinical relevance. These data highlight the differences between primary breast cancers and brain metastases and the importance of acquiring and analysing brain metastasis samples for further study"

"The two most commonly reported genes in both extracranial studies and in this Review were TP53 and PIK3CA".

"Because TP53 mutations were reported in 85 (52%) and PIK3CA mutations were reported in 36 (22%) of the 164 breast cancer brain metastases, these two genes represent the most obvious targets for intervention. PI3Kalpha-specific inhibitor alpelisib has shown activity in PIK3CA-mutated breast cancer.41 The brain penetrant inhibitor paxalisib (GDC-0084) has shown activity in preclinical models of breast cancer brain metastasis42 and preliminary clinical activity in glioblastoma,43 and there are several ongoing clinical trials in patients with breast cancer and brain metastases (appendix pp 4–5)".

"Conclusion
To our knowledge, this systematic Review is the first to examine the genomic landscape of brain metastases from breast cancer and combine multiple smaller studies to produce more convincing and powerful findings. Several of the commonly mutated genes in breast cancer brain metastases present potential therapeutic targets. Furthermore, receptor status switching between the primary breast cancer and the brain metastasis suggests a genomic divergence that might also present new avenues for treatment in addition to current challenges".

I await the interim data results from Danna-Farber combination trial and ALLIANCE trial.

https://www.researchgate.net/publication/348033458_The_genomic_landscape_of_breast_cancer_brain_metastases_a_systematic_review

Regards.