Investigation of molecular alterations of AKT‐3 in triple‐negative breast cancer. Issue 5 (12th December 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Histopathology. Volume 64:Issue 5(2014)
• Page Start: 660
• Page End: 670
• Publication Date: 2013-12-12
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12313
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12313-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12313-sec-0001" sec-type="section"> <title>Aims</title> <p>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 <italic>AKT‐3</italic> was previously reported in oestrogen receptor (ER)‐positive BC. <italic>AKT‐3</italic> has also been suggested to play a role in hormone‐unresponsive BC. The aim of this study was to investigate molecular alterations of <italic>AKT‐3</italic> in TNBC, to perform associated survival analysis, and to compare these findings with the incidence of <italic>AKT‐3</italic> molecular alterations in ER‐positive BC.</p> </sec> <sec id="his12313-sec-0002" sec-type="section"> <title>Results</title> <p>Our study revealed <italic>AKT‐3</italic> 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 <italic>AKT‐3</italic> amplifications and deletions. A higher prevalence of <italic>AKT‐3</italic> copy number gains was observed in TNBC [26% (21/82)] than in ER‐positive BC [9% (19/209)]. <italic>AKT‐3</italic> amplification together with Akt‐3 protein expression was negatively associated with recurrence‐free survival in TNBC. Furthermore, a negative association between high <italic>AKT‐3</italic> copy number and recurrence‐free survival was observed.</p> </sec> <sec id="his12313-sec-0003" sec-type="section"> <title>Conclusion</title> <p> <italic>AKT‐3</italic> amplification could represent a potentially relevant oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to Akt‐3 inhibitors.</p> </sec> </abstract>