Giannoudis, Athina 
ORCID: 0000-0002-7200-1497, Sartori, Alexander, Eastoe, Lee, Zakaria, Rasheed ORCID: 0000-0001-6826-2662, Charlton, Christopher, Hickson, Nicholas, Platt-Higgins, Angela, Rudland, Philip S ORCID: 0000-0002-7491-0846, Irwin, Darryl, Jenkinson, Michael D ORCID: 0000-0003-4587-2139 et al (show 1 more authors)
(2021)
Genomic profiling using the UltraSEEK panel identifies discordancy between paired primary and breast cancer brain metastases and an association with brain metastasis-free survival.
BREAST CANCER RESEARCH AND TREATMENT, 190 (2).
pp. 241-253.
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Giannoudis et al 2021.pdf - Published version Download (3MB) | Preview |
Abstract
<h4>Purpose</h4>Brain metastases (BM) are an increasing clinical problem. This study aimed to assess paired primary breast cancers (BC) and BM for aberrations within TP53, PIK3CA, ESR1, ERBB2 and AKT utilising the MassARRAY® UltraSEEK® technology (Agena Bioscience, San Diego, USA).<h4>Methods</h4>DNA isolated from 32 paired primary BCs and BMs was screened using the custom UltraSEEK® Breast Cancer Panel. Data acquisition and analysis was performed by the Agena Bioscience Typer software v4.0.26.74.<h4>Results</h4>Mutations were identified in 91% primary BCs and 88% BM cases. TP53, AKT1, ESR1, PIK3CA and ERBB2 genes were mutated in 68.8%, 37.5%, 31.3%, 28.1% and 3.1% respectively of primary BCs and in 59.4%, 37.5%, 28.1%, 28.1% and 3.1% respectively of BMs. Differences in the mutations within the 5 genes between BC and paired BM were identified in 62.5% of paired cases. In primary BCs, ER-positive/HER2-negative cases harboured the most mutations (70%), followed by ER-positive/HER2-positive (15%) and triple-negatives (13.4%), whereas in BMs, the highest number of mutations was observed in triple-negative (52.5%), followed by ER-positive/HER2-negative (35.6%) and ER-negative/HER2-positive (12%). There was a significant association between the number of mutations in the primary BC and breast-to-brain metastasis-free survival (p = 0.0001) but not with overall survival (p = 0.056).<h4>Conclusion</h4>These data demonstrate the discordancy between primary BC and BM, as well as the presence of clinically important, actionable mutations in BCBM. The UltraSEEK® Breast Cancer Panel provides a tool for BCBM that can be utilised to direct more tailored treatment decisions and for clinical studies investigating targeted agents.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | UltraSEEK (R), Mutations, Breast cancer, Brain metastasis |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Clinical Directorate Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Sep 2021 07:41 |
| Last Modified: | 07 Feb 2023 17:23 |
| DOI: | 10.1007/s10549-021-06364-8 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3137694 |
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