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Investigation of molecular alterations of AKT ‐3 in triple‐negative breast cancer
Author(s) -
O'Hurley Gillian,
Daly Etáin,
O'Grady Anthony,
Cummins Robert,
Quinn Cecily,
Flanagan Louise,
Pierce Aisling,
Fan Yue,
Lynn Miriam A,
Rafferty Máirín,
Fitzgerald Dara,
Pontén Fredrik,
Duffy Michael J,
Jirström Karin,
Kay Elaine W,
Gallagher William M
Publication year - 2014
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12313
Subject(s) - protein kinase b , triple negative breast cancer , breast cancer , cancer research , cancer , gene duplication , medicine , oncology , biology , gene , phosphorylation , genetics
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 TNBC s, respectively. In contrast, 1% (2/209) of ER ‐positive BC s 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 TNBC s that may, in turn, select cells sensitive to Akt‐3 inhibitors.