Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors

Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Oncology research and treatment 2022-05, Vol.45 (5), p.248-253
Hauptverfasser: Decker, Thomas, Bichler, Matthias, Birtel, Andrea, Fischer, Gerhard, Geiger, Kathrin, Gaenger, Stella, Nonnenbroich, Christoph, Dechow, Tobias, Muendlein, Axel
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 253
container_issue 5
container_start_page 248
container_title Oncology research and treatment
container_volume 45
creator Decker, Thomas
Bichler, Matthias
Birtel, Andrea
Fischer, Gerhard
Geiger, Kathrin
Gaenger, Stella
Nonnenbroich, Christoph
Dechow, Tobias
Muendlein, Axel
description Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in patients treated with chemotherapy (chemo) or CDK4/6 inhibitors given with endocrine treatment (CE treatment). Methods: We performed a prospective analysis of circulating tumor DNA (ctDNA) by targeted next-generation sequencing in 46 patients before the beginning of a systemic first-line (n = 37) or second-line (n = 9) treatment. Ct DNA was analyzed again upon disease progression. Results: New mutations in ctDNA of patients with progressive disease were detected in 1/11 patients who started chemo, in 4/9 patients treated with chemo followed by CE maintenance treatment, and in 9/26 patients receiving CE therapy. The number of acquired new mutations did not differ significantly between the three therapy cohorts (all p values >0.05). However, in patients classified as secondary resistant (n = 37), occurrence of new mutations significantly differed between patients who started chemo (0/9) compared to patients treated with chemo followed by CE (4/11; p = 0.041) and patients receiving CE therapy (8/19; p = 0.024), respectively. Conclusion: Clonal evolution might differ significantly between metastatic breast cancer patients with hormone receptor positive and HER-2 negative disease treated with chemo or CDK4/6 inhibitors. These results should be confirmed in larger patient cohorts.
doi_str_mv 10.1159/000523758
format Article
fullrecord <record><control><sourceid>proquest_karge</sourceid><recordid>TN_cdi_karger_primary_523758</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2634547550</sourcerecordid><originalsourceid>FETCH-LOGICAL-c369t-56406f24f2e5a0c24333645453ced8ef35a6326ad31a63bfff12c76f241481783</originalsourceid><addsrcrecordid>eNptkE1P3DAQhi3UChDlwB0hS1xAaoo_Yic5Qli6qAjQajlH3mTMGpI42F4Q_4CfXa-y3VNP8470zDPSi9ARJb8oFcUFIUQwnol8B-0zVshEMMm-bXNG9tCh9y8Ro0yIPCt20R4XjBFOin30Vba2Vy2evNt2FYztsenxowoG-uDxhwlLPLWusz3gGdQwBOvwo_UmmHf4iaeTWcLwPTyr9Y6vHCgfcKn6Ghyexy1AM0rKJXQ2LMGp4RNHR3n9J72Q-LZfmoWJUv8Dfdeq9XC4mQfo6WYyL6fJ3cPv2_LyLqm5LEIiZEqkZqlmIBSpWco5l6lIBa-hyUFzoSRnUjWcxrDQWlNWZ-sLmuY0y_kBOhu9g7NvK_Ch6oyvoW1VD3blKyZ51GVCkIiej2jtrPcOdDU40yn3WVFSrbuvtt1H9mSjXS06aLbkv6YjcDoCr8o9g9sCD7P5qKiGRkfq-L_U5stf746SMg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2634547550</pqid></control><display><type>article</type><title>Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors</title><source>MEDLINE</source><source>Karger Journals Complete</source><source>Alma/SFX Local Collection</source><creator>Decker, Thomas ; Bichler, Matthias ; Birtel, Andrea ; Fischer, Gerhard ; Geiger, Kathrin ; Gaenger, Stella ; Nonnenbroich, Christoph ; Dechow, Tobias ; Muendlein, Axel</creator><creatorcontrib>Decker, Thomas ; Bichler, Matthias ; Birtel, Andrea ; Fischer, Gerhard ; Geiger, Kathrin ; Gaenger, Stella ; Nonnenbroich, Christoph ; Dechow, Tobias ; Muendlein, Axel</creatorcontrib><description>Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in patients treated with chemotherapy (chemo) or CDK4/6 inhibitors given with endocrine treatment (CE treatment). Methods: We performed a prospective analysis of circulating tumor DNA (ctDNA) by targeted next-generation sequencing in 46 patients before the beginning of a systemic first-line (n = 37) or second-line (n = 9) treatment. Ct DNA was analyzed again upon disease progression. Results: New mutations in ctDNA of patients with progressive disease were detected in 1/11 patients who started chemo, in 4/9 patients treated with chemo followed by CE maintenance treatment, and in 9/26 patients receiving CE therapy. The number of acquired new mutations did not differ significantly between the three therapy cohorts (all p values &gt;0.05). However, in patients classified as secondary resistant (n = 37), occurrence of new mutations significantly differed between patients who started chemo (0/9) compared to patients treated with chemo followed by CE (4/11; p = 0.041) and patients receiving CE therapy (8/19; p = 0.024), respectively. Conclusion: Clonal evolution might differ significantly between metastatic breast cancer patients with hormone receptor positive and HER-2 negative disease treated with chemo or CDK4/6 inhibitors. These results should be confirmed in larger patient cohorts.</description><identifier>ISSN: 2296-5270</identifier><identifier>EISSN: 2296-5262</identifier><identifier>DOI: 10.1159/000523758</identifier><identifier>PMID: 35220309</identifier><language>eng</language><publisher>Basel, Switzerland</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Circulating Tumor DNA - genetics ; Clonal Evolution ; Cyclin-Dependent Kinase 4 - genetics ; Cyclin-Dependent Kinase 4 - therapeutic use ; Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors ; Female ; Humans ; Receptor, ErbB-2 - genetics ; Research Article ; Triple Negative Breast Neoplasms - drug therapy</subject><ispartof>Oncology research and treatment, 2022-05, Vol.45 (5), p.248-253</ispartof><rights>2022 S. Karger AG, Basel</rights><rights>2022 S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-56406f24f2e5a0c24333645453ced8ef35a6326ad31a63bfff12c76f241481783</citedby><cites>FETCH-LOGICAL-c369t-56406f24f2e5a0c24333645453ced8ef35a6326ad31a63bfff12c76f241481783</cites><orcidid>0000-0002-5582-4125 ; 0000-0003-3814-8775</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35220309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Decker, Thomas</creatorcontrib><creatorcontrib>Bichler, Matthias</creatorcontrib><creatorcontrib>Birtel, Andrea</creatorcontrib><creatorcontrib>Fischer, Gerhard</creatorcontrib><creatorcontrib>Geiger, Kathrin</creatorcontrib><creatorcontrib>Gaenger, Stella</creatorcontrib><creatorcontrib>Nonnenbroich, Christoph</creatorcontrib><creatorcontrib>Dechow, Tobias</creatorcontrib><creatorcontrib>Muendlein, Axel</creatorcontrib><title>Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors</title><title>Oncology research and treatment</title><addtitle>Oncol Res Treat</addtitle><description>Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in patients treated with chemotherapy (chemo) or CDK4/6 inhibitors given with endocrine treatment (CE treatment). Methods: We performed a prospective analysis of circulating tumor DNA (ctDNA) by targeted next-generation sequencing in 46 patients before the beginning of a systemic first-line (n = 37) or second-line (n = 9) treatment. Ct DNA was analyzed again upon disease progression. Results: New mutations in ctDNA of patients with progressive disease were detected in 1/11 patients who started chemo, in 4/9 patients treated with chemo followed by CE maintenance treatment, and in 9/26 patients receiving CE therapy. The number of acquired new mutations did not differ significantly between the three therapy cohorts (all p values &gt;0.05). However, in patients classified as secondary resistant (n = 37), occurrence of new mutations significantly differed between patients who started chemo (0/9) compared to patients treated with chemo followed by CE (4/11; p = 0.041) and patients receiving CE therapy (8/19; p = 0.024), respectively. Conclusion: Clonal evolution might differ significantly between metastatic breast cancer patients with hormone receptor positive and HER-2 negative disease treated with chemo or CDK4/6 inhibitors. These results should be confirmed in larger patient cohorts.</description><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Clonal Evolution</subject><subject>Cyclin-Dependent Kinase 4 - genetics</subject><subject>Cyclin-Dependent Kinase 4 - therapeutic use</subject><subject>Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors</subject><subject>Female</subject><subject>Humans</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Research Article</subject><subject>Triple Negative Breast Neoplasms - drug therapy</subject><issn>2296-5270</issn><issn>2296-5262</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1P3DAQhi3UChDlwB0hS1xAaoo_Yic5Qli6qAjQajlH3mTMGpI42F4Q_4CfXa-y3VNP8470zDPSi9ARJb8oFcUFIUQwnol8B-0zVshEMMm-bXNG9tCh9y8Ro0yIPCt20R4XjBFOin30Vba2Vy2evNt2FYztsenxowoG-uDxhwlLPLWusz3gGdQwBOvwo_UmmHf4iaeTWcLwPTyr9Y6vHCgfcKn6Ghyexy1AM0rKJXQ2LMGp4RNHR3n9J72Q-LZfmoWJUv8Dfdeq9XC4mQfo6WYyL6fJ3cPv2_LyLqm5LEIiZEqkZqlmIBSpWco5l6lIBa-hyUFzoSRnUjWcxrDQWlNWZ-sLmuY0y_kBOhu9g7NvK_Ch6oyvoW1VD3blKyZ51GVCkIiej2jtrPcOdDU40yn3WVFSrbuvtt1H9mSjXS06aLbkv6YjcDoCr8o9g9sCD7P5qKiGRkfq-L_U5stf746SMg</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Decker, Thomas</creator><creator>Bichler, Matthias</creator><creator>Birtel, Andrea</creator><creator>Fischer, Gerhard</creator><creator>Geiger, Kathrin</creator><creator>Gaenger, Stella</creator><creator>Nonnenbroich, Christoph</creator><creator>Dechow, Tobias</creator><creator>Muendlein, Axel</creator><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><orcidid>https://orcid.org/0000-0002-5582-4125</orcidid><orcidid>https://orcid.org/0000-0003-3814-8775</orcidid></search><sort><creationdate>20220501</creationdate><title>Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors</title><author>Decker, Thomas ; Bichler, Matthias ; Birtel, Andrea ; Fischer, Gerhard ; Geiger, Kathrin ; Gaenger, Stella ; Nonnenbroich, Christoph ; Dechow, Tobias ; Muendlein, Axel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-56406f24f2e5a0c24333645453ced8ef35a6326ad31a63bfff12c76f241481783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Clonal Evolution</topic><topic>Cyclin-Dependent Kinase 4 - genetics</topic><topic>Cyclin-Dependent Kinase 4 - therapeutic use</topic><topic>Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors</topic><topic>Female</topic><topic>Humans</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Research Article</topic><topic>Triple Negative Breast Neoplasms - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Decker, Thomas</creatorcontrib><creatorcontrib>Bichler, Matthias</creatorcontrib><creatorcontrib>Birtel, Andrea</creatorcontrib><creatorcontrib>Fischer, Gerhard</creatorcontrib><creatorcontrib>Geiger, Kathrin</creatorcontrib><creatorcontrib>Gaenger, Stella</creatorcontrib><creatorcontrib>Nonnenbroich, Christoph</creatorcontrib><creatorcontrib>Dechow, Tobias</creatorcontrib><creatorcontrib>Muendlein, Axel</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>Oncology research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Decker, Thomas</au><au>Bichler, Matthias</au><au>Birtel, Andrea</au><au>Fischer, Gerhard</au><au>Geiger, Kathrin</au><au>Gaenger, Stella</au><au>Nonnenbroich, Christoph</au><au>Dechow, Tobias</au><au>Muendlein, Axel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors</atitle><jtitle>Oncology research and treatment</jtitle><addtitle>Oncol Res Treat</addtitle><date>2022-05-01</date><risdate>2022</risdate><volume>45</volume><issue>5</issue><spage>248</spage><epage>253</epage><pages>248-253</pages><issn>2296-5270</issn><eissn>2296-5262</eissn><abstract>Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in patients treated with chemotherapy (chemo) or CDK4/6 inhibitors given with endocrine treatment (CE treatment). Methods: We performed a prospective analysis of circulating tumor DNA (ctDNA) by targeted next-generation sequencing in 46 patients before the beginning of a systemic first-line (n = 37) or second-line (n = 9) treatment. Ct DNA was analyzed again upon disease progression. Results: New mutations in ctDNA of patients with progressive disease were detected in 1/11 patients who started chemo, in 4/9 patients treated with chemo followed by CE maintenance treatment, and in 9/26 patients receiving CE therapy. The number of acquired new mutations did not differ significantly between the three therapy cohorts (all p values &gt;0.05). However, in patients classified as secondary resistant (n = 37), occurrence of new mutations significantly differed between patients who started chemo (0/9) compared to patients treated with chemo followed by CE (4/11; p = 0.041) and patients receiving CE therapy (8/19; p = 0.024), respectively. Conclusion: Clonal evolution might differ significantly between metastatic breast cancer patients with hormone receptor positive and HER-2 negative disease treated with chemo or CDK4/6 inhibitors. These results should be confirmed in larger patient cohorts.</abstract><cop>Basel, Switzerland</cop><pmid>35220309</pmid><doi>10.1159/000523758</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-5582-4125</orcidid><orcidid>https://orcid.org/0000-0003-3814-8775</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2296-5270
ispartof Oncology research and treatment, 2022-05, Vol.45 (5), p.248-253
issn 2296-5270
2296-5262
language eng
recordid cdi_karger_primary_523758
source MEDLINE; Karger Journals Complete; Alma/SFX Local Collection
subjects Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Circulating Tumor DNA - genetics
Clonal Evolution
Cyclin-Dependent Kinase 4 - genetics
Cyclin-Dependent Kinase 4 - therapeutic use
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
Female
Humans
Receptor, ErbB-2 - genetics
Research Article
Triple Negative Breast Neoplasms - drug therapy
title Clonal Evolution in Patients with Hormone Receptor Positive, HER-2 Negative Breast Cancer Treated with Chemotherapy or CDK4/6 Inhibitors
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T04%3A25%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_karge&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clonal%20Evolution%20in%20Patients%20with%20Hormone%20Receptor%20Positive,%20HER-2%20Negative%20Breast%20Cancer%20Treated%20with%20Chemotherapy%20or%20CDK4/6%20Inhibitors&rft.jtitle=Oncology%20research%20and%20treatment&rft.au=Decker,%20Thomas&rft.date=2022-05-01&rft.volume=45&rft.issue=5&rft.spage=248&rft.epage=253&rft.pages=248-253&rft.issn=2296-5270&rft.eissn=2296-5262&rft_id=info:doi/10.1159/000523758&rft_dat=%3Cproquest_karge%3E2634547550%3C/proquest_karge%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2634547550&rft_id=info:pmid/35220309&rfr_iscdi=true