Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer
Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response...
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description | Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS™) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the ‘pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways. |
doi_str_mv | 10.1007/s10549-010-0747-9 |
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Michael ; Armstrong, Anne C ; Howell, Sacha ; Renshaw, Lorna ; Donald, Emma ; Greystoke, Alastair ; Ranson, Malcolm ; Hughes, Andrew ; Dive, Caroline</creator><creatorcontrib>Board, Ruth E ; Wardley, Andrew M ; Dixon, J. Michael ; Armstrong, Anne C ; Howell, Sacha ; Renshaw, Lorna ; Donald, Emma ; Greystoke, Alastair ; Ranson, Malcolm ; Hughes, Andrew ; Dive, Caroline</creatorcontrib><description>Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS™) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the ‘pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-010-0747-9</identifier><identifier>PMID: 20107891</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Biomarkers ; Breast cancer ; Breast Neoplasms - blood ; Breast Neoplasms - genetics ; Cancer ; Cancer patients ; Cancer research ; Cancer therapies ; Care and treatment ; Class I Phosphatidylinositol 3-Kinases ; Clinical Trial ; Clinical trials ; Deoxyribonucleic acid ; DNA ; DNA - blood ; DNA - genetics ; DNA Mutational Analysis ; Female ; Genes ; Genetic aspects ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; Oncology ; Phosphatidylinositol 3-Kinases - genetics ; Tumors</subject><ispartof>Breast cancer research and treatment, 2010-04, Vol.120 (2), p.461-467</ispartof><rights>Springer Science+Business Media, LLC. 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c597t-e760ab855d1afed2a3c8e4b091f22f2e2b5b76ca0b5629cc3ae5fdf3d55662193</citedby><cites>FETCH-LOGICAL-c597t-e760ab855d1afed2a3c8e4b091f22f2e2b5b76ca0b5629cc3ae5fdf3d55662193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-010-0747-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-010-0747-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22582218$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20107891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Board, Ruth E</creatorcontrib><creatorcontrib>Wardley, Andrew M</creatorcontrib><creatorcontrib>Dixon, J. Michael</creatorcontrib><creatorcontrib>Armstrong, Anne C</creatorcontrib><creatorcontrib>Howell, Sacha</creatorcontrib><creatorcontrib>Renshaw, Lorna</creatorcontrib><creatorcontrib>Donald, Emma</creatorcontrib><creatorcontrib>Greystoke, Alastair</creatorcontrib><creatorcontrib>Ranson, Malcolm</creatorcontrib><creatorcontrib>Hughes, Andrew</creatorcontrib><creatorcontrib>Dive, Caroline</creatorcontrib><title>Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS™) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the ‘pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - genetics</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Class I Phosphatidylinositol 3-Kinases</subject><subject>Clinical Trial</subject><subject>Clinical trials</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - blood</subject><subject>DNA - genetics</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Gynecology. 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Michael ; Armstrong, Anne C ; Howell, Sacha ; Renshaw, Lorna ; Donald, Emma ; Greystoke, Alastair ; Ranson, Malcolm ; Hughes, Andrew ; Dive, Caroline</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c597t-e760ab855d1afed2a3c8e4b091f22f2e2b5b76ca0b5629cc3ae5fdf3d55662193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - blood</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Class I Phosphatidylinositol 3-Kinases</topic><topic>Clinical Trial</topic><topic>Clinical trials</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - blood</topic><topic>DNA - genetics</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Board, Ruth E</creatorcontrib><creatorcontrib>Wardley, Andrew M</creatorcontrib><creatorcontrib>Dixon, J. 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Michael</au><au>Armstrong, Anne C</au><au>Howell, Sacha</au><au>Renshaw, Lorna</au><au>Donald, Emma</au><au>Greystoke, Alastair</au><au>Ranson, Malcolm</au><au>Hughes, Andrew</au><au>Dive, Caroline</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2010-04-01</date><risdate>2010</risdate><volume>120</volume><issue>2</issue><spage>461</spage><epage>467</epage><pages>461-467</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS™) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the ‘pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>20107891</pmid><doi>10.1007/s10549-010-0747-9</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Biological and medical sciences Biomarkers Breast cancer Breast Neoplasms - blood Breast Neoplasms - genetics Cancer Cancer patients Cancer research Cancer therapies Care and treatment Class I Phosphatidylinositol 3-Kinases Clinical Trial Clinical trials Deoxyribonucleic acid DNA DNA - blood DNA - genetics DNA Mutational Analysis Female Genes Genetic aspects Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical sciences Medicine Medicine & Public Health Middle Aged Mutation Oncology Phosphatidylinositol 3-Kinases - genetics Tumors |
title | Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer |
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