Phosphatidylinositol 3-kinase (PI3K) pathway activation in breast cancer brain metastases
Menée sur 52 métastases cérébrales de cancer du sein et 12 tumeurs primitives correspondantes, cette étude identifie l'activation de la voie de signalisation PI3K dans la plupart des métastases indépendamment du sous-type de cancer du sein
INTRODUCTION:Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBM) is largely unknown. We examined expression of phospho(p)-AKT, p-S6 and phosphatase and tensin homolog (PTEN) in breast cancer brain metastases (BCBM) and their implications for overall survival (OS) and survival following BCBM. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBM. Similar analyses were also conducted among the subset of patients with triple negative BCBM.METHODS:p-AKT, p-S6, and PTEN expression was assessed via immunohistochemistry in 52 BCBM and 12 matched primary BC. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+ and triple-negative (TNBC). Survival analyses were performed using a Cox model and survival curves were estimated by the Kaplan-Meier method.RESULTS:Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69% and 25% of BCBM. Concordance between primary BC and matched BCBM was 67% for p-AKT, 58% for p-S6 and 83% for PTEN. PTEN- was more common in TNBC compared to HR+/HER2- and HER2+. Expression of p-AKT, p-S6 and PTEN- was not associated with OS or survival following BCBM (all, P>0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBM was associated with poorer overall survival.CONCLUSIONS:The PI3K pathway is active in most BCBM regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBM, a group of patients with poor prognosis and limited systemic therapeutic options. While expression of the PI3K pathway did not correlate with OS and survival following BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study.