Phosphorylated S6 kinase-1: a breast cancer marker predicting resistance to neoadjuvant chemotherapy.

Abstract

BACKGROUND: Pre-clinical data support a link between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and chemoresponsiveness. We evaluated whether the expression of phosphorylated AKT (p-AKT) or phosphorylated S6 kinase-1 (p-S6K1), a key effector of the mTOR pathway, could be a predictive marker for chemoresponsiveness in breast cancer. PATIENTS AND METHODS: A total of 209 patients with locally advanced breast cancer who received neoadjuvant chemotherapy between April 2005 and July 2012 were analyzed. Patients without a minimum of 10% tumor reduction, after neoadjuvent chemotherapy, were classified as non-responders. RESULTS: Overall, 184 (88%) patients were classified as responders and 25 (12%) as non-responders. The positive expression rate for p-AKT and p-S6K1 was 31.6% and 45%, respectively. There was no difference in the pre-chemotherapy clinical stage according to p-S6K1 or p-AKT expression status. p-AKT expression was slightly higher in non-responders compared to responders (48% vs. 30.9%; p=0.088). However, p-S6K1 expression was significantly higher in non-responders than responders (68% vs. 41.8%; p=0014). Following multivariate analysis, p-S6K1 positivity remained an independent predictor of non-responder status (hazard ratio=3.81; 95% confidence interval=1.28-11.31; p=0.016). CONCLUSION: The expression of p-S6K1 may be a predictive marker of resistance to neoadjuvant chemotherapy in patients with breast cancer.