title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  The expression of p-S6K1 may be a predictive marker of resistance to neoadjuvant chemotherapy in patients with breast cancer.
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu 139-706, Seoul, Korea. nohwoo@kcch.re.kr.
authors.forename: Eun-Kyu
authors.initials: EK
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Hyesil
authors.initials: H
authors.lastname: Seol
authors.forename: Min-Ki
authors.initials: MK
authors.lastname: Seong
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jangmoo
authors.initials: J
authors.lastname: Byeon
authors.forename: Yeun Ju
authors.initials: YJ
authors.lastname: Sohn
authors.forename: Jae Soo
authors.initials: JS
authors.lastname: Koh
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Woo Chul
authors.initials: WC
authors.lastname: Noh
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: AKT; Breast cancer; S6 kinase 1 (S6K1); chemoresponsiveness; neoadjuvant chemotherapy