Investigation of molecular alterations of AKT-3 in triple-negative breast cancer
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Published on: March 20, 2020
Gillian O'Hurley1, Etáin Daly, Anthony O'Grady
1OncoMark Ltd, NovaUCD, Belfield Innovation Park, Belfield, Ireland.
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.
Insights
AKT-3 gene alterations, including amplification and deletions, are more common in triple-negative breast cancer (TNBC) than ER-positive breast cancer. These AKT-3 alterations are linked to poorer recurrence-free survival in TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressiveness and limited targeted therapy options.
- Molecular alterations in AKT-3 have been implicated in estrogen receptor-positive breast cancer and hormone-unresponsive breast cancer.
Purpose of the Study:
- To investigate molecular alterations of AKT-3 in TNBC.
- To conduct survival analysis associated with AKT-3 alterations in TNBC.
- To compare AKT-3 alterations in TNBC with those in estrogen receptor-positive breast cancer.
Main Methods:
- Analysis of AKT-3 gene copy number alterations (amplification, deletion, copy number gain) in TNBC and ER-positive breast cancer cohorts.
- Assessment of the association between AKT-3 alterations and protein expression with recurrence-free survival in TNBC.
Main Results:
- AKT-3 amplification and deletions were observed in 11% and 13% of TNBCs, respectively, compared to 1% in ER-positive breast cancer.
- Copy number gains of AKT-3 were significantly higher in TNBC (26%) than in ER-positive breast cancer (9%).
- AKT-3 amplification and high copy number were negatively associated with recurrence-free survival in TNBC patients.
Conclusions:
- AKT-3 amplification represents a potential oncogenic event in a subset of TNBC.
- These findings suggest that AKT-3 alterations may identify TNBC patients who could benefit from Akt-3 inhibitors.
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