title: Investigation of molecular alterations of AKT-3 in triple-negative breast cancer.
abstract: OBJECTIVE
  Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer (BC) deaths, owing to its intrinsic aggressiveness and a lack of treatment options, especially targeted therapies. Thus, there is an urgent need for the development of better targeted treatments for TNBC. Molecular alteration of AKT-3 was previously reported in oestrogen receptor (ER)-positive BC. AKT-3 has also been suggested to play a role in hormone-unresponsive BC. The aim of this study was to investigate molecular alterations of AKT-3 in TNBC, to perform associated survival analysis, and to compare these findings with the incidence of AKT-3 molecular alterations in ER-positive BC.
  
  
  RESULTS
  Our study revealed AKT-3 amplification and deletions in 11% (9/82) and 13% (11/82) of TNBCs, respectively. In contrast, 1% (2/209) of ER-positive BCs were found to have AKT-3 amplifications and deletions. A higher prevalence of AKT-3 copy number gains was observed in TNBC [26% (21/82)] than in ER-positive BC [9% (19/209)]. AKT-3 amplification together with Akt-3 protein expression was negatively associated with recurrence-free survival in TNBC. Furthermore, a negative association between high AKT-3 copy number and recurrence-free survival was observed.
  
  
  CONCLUSIONS
  AKT-3 amplification could represent a potentially relevant oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to Akt-3 inhibitors.
authors.affiliation: OncoMark Ltd, NovaUCD, Belfield Innovation Park, Belfield, Ireland.
authors.forename: Gillian
authors.initials: G
authors.lastname: O'Hurley
authors.forename: Etáin
authors.initials: E
authors.lastname: Daly
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Grady
authors.forename: Robert
authors.initials: R
authors.lastname: Cummins
authors.forename: Cecily
authors.initials: C
authors.lastname: Quinn
authors.forename: Louise
authors.initials: L
authors.lastname: Flanagan
authors.forename: Aisling
authors.initials: A
authors.lastname: Pierce
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Lynn
authors.forename: Máirín
authors.initials: M
authors.lastname: Rafferty
authors.forename: Dara
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duffy
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT-3; ER-positive breast cancer; fluorescence in-situ hybridization; molecular alterations; triple-negative breast cancer