Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

Abstract Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-hou...

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Autores principales:	Kanako Hagio, Toraji Amano, Hideyuki Hayashi, Takashi Takeshita, Tomohiro Oshino, Junko Kikuchi, Yoshihito Ohhara, Ichiro Yabe, Ichiro Kinoshita, Hiroshi Nishihara, Hiroko Yamashita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bcd6587139f6496c8776ae366ad162a1
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spelling	oai:doaj.org-article:bcd6587139f6496c8776ae366ad162a12021-12-02T18:03:07ZImpact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer10.1038/s41598-021-87645-62045-2322https://doaj.org/article/bcd6587139f6496c8776ae366ad162a12021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87645-6https://doaj.org/toc/2045-2322Abstract Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients’ prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.Kanako HagioToraji AmanoHideyuki HayashiTakashi TakeshitaTomohiro OshinoJunko KikuchiYoshihito OhharaIchiro YabeIchiro KinoshitaHiroshi NishiharaHiroko YamashitaNature 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 Kanako Hagio Toraji Amano Hideyuki Hayashi Takashi Takeshita Tomohiro Oshino Junko Kikuchi Yoshihito Ohhara Ichiro Yabe Ichiro Kinoshita Hiroshi Nishihara Hiroko Yamashita Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
description	Abstract Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients’ prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.
format	article
author	Kanako Hagio Toraji Amano Hideyuki Hayashi Takashi Takeshita Tomohiro Oshino Junko Kikuchi Yoshihito Ohhara Ichiro Yabe Ichiro Kinoshita Hiroshi Nishihara Hiroko Yamashita
author_facet	Kanako Hagio Toraji Amano Hideyuki Hayashi Takashi Takeshita Tomohiro Oshino Junko Kikuchi Yoshihito Ohhara Ichiro Yabe Ichiro Kinoshita Hiroshi Nishihara Hiroko Yamashita
author_sort	Kanako Hagio
title	Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
title_short	Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
title_full	Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
title_fullStr	Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
title_full_unstemmed	Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
title_sort	impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, her2-negative metastatic breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bcd6587139f6496c8776ae366ad162a1
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Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

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