title: Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in hormone receptor-positive breast cancer.
abstract: Cross-talk between the estrogen receptor and the mammalian target of rapamycin (mTOR) pathway is one of the mechanisms of endocrine therapy resistance, and the phosphorylated S6 kinase 1(p-S6K1) is known to be a marker of the mTOR pathway activation. The authors assessed the prognostic significance of p-S6K1 according to the hormone receptor (HR) status. The expression of p-S6K1 was evaluated in 304 breast cancer tissues, and the association between its expression and patient outcomes was investigated. Among 197 cases with the HR (+) tumor, 70 (35.5%) were positive for p-S6K1. Most of the patients (97.5%) with the HR (+) tumor received adjuvant endocrine therapy. The expression of p-S6K1 was found to be an independent worse prognosticator affecting overall survival (OS) and breast cancer-specific survival (BCSS) in the HR (+) group (hazard ratio, 2.62; 95% confidence interval [CI], 1.19-5.76; P = 0.017 and hazard ratio, 3.25; 95% CI, 1.20-8.82; P = 0.020, respectively). In the HR (-) group, however, the p-S6K1 expression was not associated with patients' survival. The expression of p-S6K1 is a worse prognostic factor in patients with HR (+) tumors. These results suggest that the p-S6K1 expression might be a marker for endocrine therapy resistance in patients with HR (+) tumors.
authors.affiliation: Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, 139-706, Korea.
authors.forename: Eun-Kyu
authors.initials: EK
authors.lastname: Kim
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Jae Soo
authors.initials: JS
authors.lastname: Koh
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Kwan-Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Jong Inn
authors.initials: JI
authors.lastname: Lee
authors.forename: Nan Mo
authors.initials: NM
authors.lastname: Moon
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ko
authors.forename: Woo Chul
authors.initials: WC
authors.lastname: Noh
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1