%0 Journal Article
%T pAKT pathway activation is associated with PIK3CA mutations and good prognosis in luminal breast cancer in contrast to p-mTOR pathway activation
%J -
%D 2019
%R https://doi.org/10.1038/s41523-019-0102-1
%X Numerous studies have focused on the PI3K/AKT/mTOR pathway in estrogen receptor positive (ER) breast cancer (BC), as a linear signal transduction pathway and reported its association with worse clinical outcomes. We developed gene signatures that reflect the level of expression of phosphorylated-Serine473-AKT (pAKT) and phosphorylated-Serine2448-mTOR (p-mTOR) separately, capturing their corresponding level of pathway activation. Our analysis revealed that the pAKT pathway activation was associated with luminal A BC while the p-mTOR pathway activation was more associated with luminal B BC (Kruskal¨CWallis test p£¿<£¿10£¿10). pAKT pathway activation was significantly associated with better outcomes (multivariable HR, 0.79; 95%CI, 0.74¨C0.85; p£¿=£¿2.5£¿¡Á£¿10£¿10) and PIK3CA mutations (p£¿=£¿0.0001) whereas p-mTOR pathway activation showed worse outcomes (multivariable HR,1.1; 95%CI, 1.1¨C1.2; p£¿=£¿9.9£¿¡Á£¿10£¿4) and associated with p53 mutations (p£¿=£¿0.04). in conclusion, our data show that pAKT and p-mTOR pathway activation have differing impact on prognosis and suggest that they are not linearly connected in luminal breast cancers
%U https://www.nature.com/articles/s41523-019-0102-1