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Investigation of molecular alterations of AKT-3 in triple-negative breast cancer

O'Hurley, Gillian; Daly, Etain; O'Grady, Anthony; Cummins, Robert; Quinn, Cecily; Flanagan, Louise; Pierce, Aisling; Fan, Yue; Lynn, Miriam A. and Rafferty, Mairin, et al. (2014) In Histopathology 64(5). p.660-670
Abstract
Aims 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... (More)
Aims 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. Conclusion 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. (Less)
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publication status
published
subject
keywords
fluorescence in-situ hybridization, AKT-3, ER-positive breast cancer, triple-negative breast cancer, molecular alterations
in
Histopathology
volume
64
issue
5
pages
660 - 670
publisher
Wiley-Blackwell
external identifiers
  • wos:000332788400007
  • scopus:84896125528
ISSN
0309-0167
DOI
10.1111/his.12313
language
English
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yes
id
5f4c31e6-a679-469a-855d-ffa6522e8de0 (old id 4439594)
date added to LUP
2014-07-01 07:44:27
date last changed
2017-08-27 03:14:47
@article{5f4c31e6-a679-469a-855d-ffa6522e8de0,
  abstract     = {Aims 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. Conclusion 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.},
  author       = {O'Hurley, Gillian and Daly, Etain and O'Grady, Anthony and Cummins, Robert and Quinn, Cecily and Flanagan, Louise and Pierce, Aisling and Fan, Yue and Lynn, Miriam A. and Rafferty, Mairin and Fitzgerald, Dara and Ponten, Fredrik and Duffy, Michael J. and Jirström, Karin and Kay, Elaine W. and Gallagher, William M.},
  issn         = {0309-0167},
  keyword      = {fluorescence in-situ hybridization,AKT-3,ER-positive breast cancer,triple-negative breast cancer,molecular alterations},
  language     = {eng},
  number       = {5},
  pages        = {660--670},
  publisher    = {Wiley-Blackwell},
  series       = {Histopathology},
  title        = {Investigation of molecular alterations of AKT-3 in triple-negative breast cancer},
  url          = {http://dx.doi.org/10.1111/his.12313},
  volume       = {64},
  year         = {2014},
}