title: Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer.
abstract: BACKGROUND
  Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and phosphorylated ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer.
  
  
  METHODS
  Primary tumors were collected from 190 patients with Stage I to III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays. Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed.
  
  
  RESULTS
  High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node positivity. Median follow-up for living patients was 96 months.
  
  
  CONCLUSIONS
  Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Huiqin
authors.initials: H
authors.lastname: Chen
authors.forename: Argun
authors.initials: A
authors.lastname: Akcakanat
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Hennessy
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Angulo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D014176:Protein Biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone