PIK3CA mutations and downstream effector p-mTOR expression: implication for prognostic factors and therapeutic targets in triple negative breast cancer.

Although PIK3CA mutations and phosphorylated mTOR (p-mTOR) expression are two main events on PI3K/Akt/mTOR pathway, limited data has reported their roles in triple negative breast cancer (TNBC). Thus, we evaluated the associations of these two biomarkers and clinicopathological characteristics and prognosis in large Chinese TNBC patients. Immunohistochemistry (IHC) analysis was used to assess p-mTOR expression level in 218 TNBC patients. Direct sequencing was applied to detect the most important hotspot regions in exons 9 and 20 of PIK3CA gene. In the TNBC cohort, mutations were identified in 11.5% cases which were associated with basal-like subtype. The somatic point mutations were independently associated with worse overall survival (HR=0.400, 95% CI: 0.193-0.830, P=0.014). As for p-mTOR expression, 47.7% of the tumors were positive and the staining was shown in cytoplasm, nuclear and perinuclear areas. There were significant differences observed in tumor size, lymph node status, and clinical stage between p-mTOR positive and p-mTOR negative cases. Notably, we found a significant association between p-mTOR expression and PIK3CA mutations. Patients with p-mTOR staining also demonstrated shorter overall survival (HR=0.710, 95% CI: 0.514-0.980, P=0.037). Therefore, PIK3CA mutations and its downstream effector p-mTOR expression were two important regulators for activating the PI3K/Akt/mTOR pathway. Both of them could be served as adverse prognostic biomarkers and may contribute to the targeted therapy for TNBC patients with poor outcome. IJCEP