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Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression o...

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Autores principales: Aradottir, Margret, Reynisdottir, Sigridur T, Stefansson, Olafur A, Jonasson, Jon G, Sverrisdottir, Asgerdur, Tryggvadottir, Laufey, Eyfjord, Jorunn E, Bodvarsdottir, Sigridur K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858119/
https://www.ncbi.nlm.nih.gov/pubmed/27499891
http://dx.doi.org/10.1002/cjp2.6
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author Aradottir, Margret
Reynisdottir, Sigridur T
Stefansson, Olafur A
Jonasson, Jon G
Sverrisdottir, Asgerdur
Tryggvadottir, Laufey
Eyfjord, Jorunn E
Bodvarsdottir, Sigridur K
author_facet Aradottir, Margret
Reynisdottir, Sigridur T
Stefansson, Olafur A
Jonasson, Jon G
Sverrisdottir, Asgerdur
Tryggvadottir, Laufey
Eyfjord, Jorunn E
Bodvarsdottir, Sigridur K
author_sort Aradottir, Margret
collection PubMed
description Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment.
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spelling pubmed-48581192016-08-05 Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers Aradottir, Margret Reynisdottir, Sigridur T Stefansson, Olafur A Jonasson, Jon G Sverrisdottir, Asgerdur Tryggvadottir, Laufey Eyfjord, Jorunn E Bodvarsdottir, Sigridur K J Pathol Clin Res Original Articles Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild‐type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer‐specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23–40.6; p = 0.028). Poor breast cancer‐specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19–85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81–51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment. John Wiley and Sons Inc. 2014-11-07 /pmc/articles/PMC4858119/ /pubmed/27499891 http://dx.doi.org/10.1002/cjp2.6 Text en © 2014 John Wiley and Sons Ltd and The Pathological Society of Great Britain and Ireland This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/3.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Aradottir, Margret
Reynisdottir, Sigridur T
Stefansson, Olafur A
Jonasson, Jon G
Sverrisdottir, Asgerdur
Tryggvadottir, Laufey
Eyfjord, Jorunn E
Bodvarsdottir, Sigridur K
Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title_full Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title_fullStr Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title_full_unstemmed Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title_short Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers
title_sort aurora a is a prognostic marker for breast cancer arising in brca2 mutation carriers
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858119/
https://www.ncbi.nlm.nih.gov/pubmed/27499891
http://dx.doi.org/10.1002/cjp2.6
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