Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu 139-706, Seoul, Korea.
Anticancer Res. 2013 Sep;33(9):4073-9.
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.
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.
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).
The expression of p-S6K1 may be a predictive marker of resistance to neoadjuvant chemotherapy in patients with breast cancer.
临床前数据支持磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路与化疗反应之间存在关联。我们评估了磷酸化 AKT（p-AKT）或磷酸化 S6 激酶-1（p-S6K1）的表达是否可以作为乳腺癌化疗反应的预测标志物，mTOR 通路的关键效应物。
分析了 209 例 2005 年 4 月至 2012 年 7 月期间接受新辅助化疗的局部晚期乳腺癌患者。新辅助化疗后肿瘤减少率低于 10%的患者被归类为无反应者。
总体而言，184 例（88%）患者被归类为有反应者，25 例（12%）患者为无反应者。p-AKT 和 p-S6K1 的阳性表达率分别为 31.6%和 45%。根据 p-S6K1 或 p-AKT 表达状态，化疗前临床分期无差异。无反应者的 p-AKT 表达略高于有反应者（48% vs. 30.9%；p=0.088）。然而，无反应者的 p-S6K1 表达明显高于有反应者（68% vs. 41.8%；p=0.0014）。多因素分析后，p-S6K1 阳性仍然是无反应状态的独立预测因子（风险比=3.81；95%置信区间=1.28-11.31；p=0.016）。
p-S6K1 的表达可能是乳腺癌患者对新辅助化疗耐药的预测标志物。
