Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients

Abstract Mutational analysis of circulating tumour (ct) DNA holds promise as an effective tool to predict the course of metastatic breast cancer (MBC). In the present study we used targeted next generation sequencing of ctDNA to evaluate the impact of cancer driven mutations on the prognosis of MBC....

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Autores principales:	Axel Muendlein, Kathrin Geiger, Stella Gaenger, Tobias Dechow, Christoph Nonnenbroich, Andreas Leiherer, Heinz Drexel, Andreas Gaumann, Wolfgang Jagla, Thomas Winder, Frank Mayer, Thomas Decker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37dd500e40fe4840b82c9e036d120298
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spelling	oai:doaj.org-article:37dd500e40fe4840b82c9e036d1202982021-12-02T17:04:06ZSignificant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients10.1038/s41598-021-86238-72045-2322https://doaj.org/article/37dd500e40fe4840b82c9e036d1202982021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86238-7https://doaj.org/toc/2045-2322Abstract Mutational analysis of circulating tumour (ct) DNA holds promise as an effective tool to predict the course of metastatic breast cancer (MBC). In the present study we used targeted next generation sequencing of ctDNA to evaluate the impact of cancer driven mutations on the prognosis of MBC. The study included 59 oestrogen receptor-positive (ER+), HER2-negative MBC patients. Sequencing analysis was performed in ESR1, PIK3CA, ERBB2, PTEN, TP53, KRAS, HRAS, NRAS, and AR. At baseline, patients started receiving either chemotherapy (34%; n = 20) or cyclin-dependent kinase 4/6 inhibitor therapy in combination with endocrine therapy (CDK4/6i+ET; 66%; n = 39). Overall, 64.4% (n = 38) of the patients carried at least one pathogenic or likely-pathogenic mutation. Number of ctDNA mutations was significantly linked with worse progression free survival (PFS; p = 0.003) and overall survival (OS; p = 0.007). Furthermore, ctDNA load, defined by the number of mutant ctDNA molecules per mL plasma, significantly correlated with PFS (p < 0.001) and OS (p = 0.001). Furthermore, mutational status of ESR1 and TP53 significantly predicted PFS (p = 0.024 and p = 0.035, respectively) and OS (p < 0.001 and p = 0.035, respectively). These results emphasizes the clinical value of ctDNA mutational analysis in the management of advanced breast cancer.Axel MuendleinKathrin GeigerStella GaengerTobias DechowChristoph NonnenbroichAndreas LeihererHeinz DrexelAndreas GaumannWolfgang JaglaThomas WinderFrank MayerThomas DeckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Axel Muendlein Kathrin Geiger Stella Gaenger Tobias Dechow Christoph Nonnenbroich Andreas Leiherer Heinz Drexel Andreas Gaumann Wolfgang Jagla Thomas Winder Frank Mayer Thomas Decker Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
description	Abstract Mutational analysis of circulating tumour (ct) DNA holds promise as an effective tool to predict the course of metastatic breast cancer (MBC). In the present study we used targeted next generation sequencing of ctDNA to evaluate the impact of cancer driven mutations on the prognosis of MBC. The study included 59 oestrogen receptor-positive (ER+), HER2-negative MBC patients. Sequencing analysis was performed in ESR1, PIK3CA, ERBB2, PTEN, TP53, KRAS, HRAS, NRAS, and AR. At baseline, patients started receiving either chemotherapy (34%; n = 20) or cyclin-dependent kinase 4/6 inhibitor therapy in combination with endocrine therapy (CDK4/6i+ET; 66%; n = 39). Overall, 64.4% (n = 38) of the patients carried at least one pathogenic or likely-pathogenic mutation. Number of ctDNA mutations was significantly linked with worse progression free survival (PFS; p = 0.003) and overall survival (OS; p = 0.007). Furthermore, ctDNA load, defined by the number of mutant ctDNA molecules per mL plasma, significantly correlated with PFS (p < 0.001) and OS (p = 0.001). Furthermore, mutational status of ESR1 and TP53 significantly predicted PFS (p = 0.024 and p = 0.035, respectively) and OS (p < 0.001 and p = 0.035, respectively). These results emphasizes the clinical value of ctDNA mutational analysis in the management of advanced breast cancer.
format	article
author	Axel Muendlein Kathrin Geiger Stella Gaenger Tobias Dechow Christoph Nonnenbroich Andreas Leiherer Heinz Drexel Andreas Gaumann Wolfgang Jagla Thomas Winder Frank Mayer Thomas Decker
author_facet	Axel Muendlein Kathrin Geiger Stella Gaenger Tobias Dechow Christoph Nonnenbroich Andreas Leiherer Heinz Drexel Andreas Gaumann Wolfgang Jagla Thomas Winder Frank Mayer Thomas Decker
author_sort	Axel Muendlein
title	Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
title_short	Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
title_full	Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
title_fullStr	Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
title_full_unstemmed	Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients
title_sort	significant impact of circulating tumour dna mutations on survival in metastatic breast cancer patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/37dd500e40fe4840b82c9e036d120298
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Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients

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