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Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer
Understanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopath...
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| Published in: | European journal of cancer (1990) 2018-01, Vol.89, p.64-71 |
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| Main Authors: | , , , , , , , , , , , , |
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| container_end_page | 71 |
| container_issue | |
| container_start_page | 64 |
| container_title | European journal of cancer (1990) |
| container_volume | 89 |
| creator | Fujii, Takeo Matsuda, Naoko Kono, Miho Harano, Kenichi Chen, Huiqin Luthra, Rajyalakshmi Roy-Chowdhuri, Sinchita Sahin, Aysegul A. Wathoo, Chetna Joon, Aron Y. Tripathy, Debu Meric-Bernstam, Funda Ueno, Naoto T. |
| description | Understanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.
Archival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P |
| doi_str_mv | 10.1016/j.ejca.2017.11.015 |
| format | article |
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Archival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.
A total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).
Systemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.
•Treatment exposure is a risk factor for high rates of TP53 and PIK3CA mutations.•The mutational status might change when patients are exposed to systemic therapy.•It is worth testing the gene profile when tumours become resistant.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2017.11.015</identifier><identifier>PMID: 29232568</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Class I Phosphatidylinositol 3-Kinases - genetics ; Female ; Genes, p53 ; Humans ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Next-generation sequencing ; PIK3CA ; Proto-Oncogene Proteins c-akt - genetics ; PTEN Phosphohydrolase - genetics ; Somatic mutations ; Systemic therapy ; TP53 ; Young Adult</subject><ispartof>European journal of cancer (1990), 2018-01, Vol.89, p.64-71</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-bff4317fba3854a89beb07fb52c12be9dcf3aaf300e0ee5292996ecd627566573</citedby><cites>FETCH-LOGICAL-c356t-bff4317fba3854a89beb07fb52c12be9dcf3aaf300e0ee5292996ecd627566573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29232568$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujii, Takeo</creatorcontrib><creatorcontrib>Matsuda, Naoko</creatorcontrib><creatorcontrib>Kono, Miho</creatorcontrib><creatorcontrib>Harano, Kenichi</creatorcontrib><creatorcontrib>Chen, Huiqin</creatorcontrib><creatorcontrib>Luthra, Rajyalakshmi</creatorcontrib><creatorcontrib>Roy-Chowdhuri, Sinchita</creatorcontrib><creatorcontrib>Sahin, Aysegul A.</creatorcontrib><creatorcontrib>Wathoo, Chetna</creatorcontrib><creatorcontrib>Joon, Aron Y.</creatorcontrib><creatorcontrib>Tripathy, Debu</creatorcontrib><creatorcontrib>Meric-Bernstam, Funda</creatorcontrib><creatorcontrib>Ueno, Naoto T.</creatorcontrib><title>Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Understanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.
Archival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.
A total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).
Systemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.
•Treatment exposure is a risk factor for high rates of TP53 and PIK3CA mutations.•The mutational status might change when patients are exposed to systemic therapy.•It is worth testing the gene profile when tumours become resistant.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Class I Phosphatidylinositol 3-Kinases - genetics</subject><subject>Female</subject><subject>Genes, p53</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Next-generation sequencing</subject><subject>PIK3CA</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>Somatic mutations</subject><subject>Systemic therapy</subject><subject>TP53</subject><subject>Young Adult</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kD9PwzAQxS0EoqXwBRiQR5YE24mdWGJBFf-kSjDAbDnORThq4mK7SP32OLQwsvh8d-896X4IXVKSU0LFTZ9Db3TOCK1ySnNC-RGa07qSGak5O0ZzIrnMalLKGToLoSeEVHVJTtGMSVYwLuo50q_eOo_DLkQYrMHRg44DjBHb0aR_gBbHD5g628JoALsOBzfomMTDNqbqxpDWeICoQ_yZN5MxYqOT3p-jk06vA1wc6gK9P9y_LZ-y1cvj8_JulZmCi5g1XVcWtOoaXdS81LVsoCGp5cxQ1oBsTVdo3RWEAAHg6QIpBZhWsIoLwatiga73uRvvPrcQohpsMLBe6xHcNigqK1EWUqRngdhearwLwUOnNt4O2u8UJWpCq3o1oVUTWkWpSmiT6eqQv20GaP8svyyT4HYvgHTllwWvgrETstZ6MFG1zv6X_w2tM4w7</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Fujii, Takeo</creator><creator>Matsuda, Naoko</creator><creator>Kono, Miho</creator><creator>Harano, Kenichi</creator><creator>Chen, Huiqin</creator><creator>Luthra, Rajyalakshmi</creator><creator>Roy-Chowdhuri, Sinchita</creator><creator>Sahin, Aysegul A.</creator><creator>Wathoo, Chetna</creator><creator>Joon, Aron Y.</creator><creator>Tripathy, Debu</creator><creator>Meric-Bernstam, Funda</creator><creator>Ueno, Naoto T.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201801</creationdate><title>Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer</title><author>Fujii, Takeo ; Matsuda, Naoko ; Kono, Miho ; Harano, Kenichi ; Chen, Huiqin ; Luthra, Rajyalakshmi ; Roy-Chowdhuri, Sinchita ; Sahin, Aysegul A. ; Wathoo, Chetna ; Joon, Aron Y. ; Tripathy, Debu ; Meric-Bernstam, Funda ; Ueno, Naoto T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-bff4317fba3854a89beb07fb52c12be9dcf3aaf300e0ee5292996ecd627566573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Class I Phosphatidylinositol 3-Kinases - genetics</topic><topic>Female</topic><topic>Genes, p53</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Next-generation sequencing</topic><topic>PIK3CA</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>Somatic mutations</topic><topic>Systemic therapy</topic><topic>TP53</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujii, Takeo</creatorcontrib><creatorcontrib>Matsuda, Naoko</creatorcontrib><creatorcontrib>Kono, Miho</creatorcontrib><creatorcontrib>Harano, Kenichi</creatorcontrib><creatorcontrib>Chen, Huiqin</creatorcontrib><creatorcontrib>Luthra, Rajyalakshmi</creatorcontrib><creatorcontrib>Roy-Chowdhuri, Sinchita</creatorcontrib><creatorcontrib>Sahin, Aysegul A.</creatorcontrib><creatorcontrib>Wathoo, Chetna</creatorcontrib><creatorcontrib>Joon, Aron Y.</creatorcontrib><creatorcontrib>Tripathy, Debu</creatorcontrib><creatorcontrib>Meric-Bernstam, Funda</creatorcontrib><creatorcontrib>Ueno, Naoto T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujii, Takeo</au><au>Matsuda, Naoko</au><au>Kono, Miho</au><au>Harano, Kenichi</au><au>Chen, Huiqin</au><au>Luthra, Rajyalakshmi</au><au>Roy-Chowdhuri, Sinchita</au><au>Sahin, Aysegul A.</au><au>Wathoo, Chetna</au><au>Joon, Aron Y.</au><au>Tripathy, Debu</au><au>Meric-Bernstam, Funda</au><au>Ueno, Naoto T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2018-01</date><risdate>2018</risdate><volume>89</volume><spage>64</spage><epage>71</epage><pages>64-71</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Understanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.
Archival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.
A total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).
Systemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.
•Treatment exposure is a risk factor for high rates of TP53 and PIK3CA mutations.•The mutational status might change when patients are exposed to systemic therapy.•It is worth testing the gene profile when tumours become resistant.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29232568</pmid><doi>10.1016/j.ejca.2017.11.015</doi><tpages>8</tpages></addata></record> |
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| ispartof | European journal of cancer (1990), 2018-01, Vol.89, p.64-71 |
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| subjects | Adolescent Adult Aged Aged, 80 and over Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - pathology Class I Phosphatidylinositol 3-Kinases - genetics Female Genes, p53 Humans Middle Aged Mutation Neoplasm Metastasis Next-generation sequencing PIK3CA Proto-Oncogene Proteins c-akt - genetics PTEN Phosphohydrolase - genetics Somatic mutations Systemic therapy TP53 Young Adult |
| title | Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer |
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