PittsburghV1, Ncbi, Curation, bibRecord, 001020

Detection of Cancer DNA in Plasma of Early Stage Breast Cancer Patients

Identifieur interne : 001020 ( Ncbi/Curation ); précédent : 001019; suivant : 001021

Detection of Cancer DNA in Plasma of Early Stage Breast Cancer Patients

Auteurs : Julia A. Beaver [États-Unis] ; Danijela Jelovac [États-Unis] ; Sasidharan Balukrishna ; Rory Cochran [États-Unis] ; Sarah Croessmann [États-Unis] ; Daniel J. Zabransky [États-Unis] ; Hong Yuen Wong [États-Unis] ; Patricia Valda Toro [États-Unis] ; Justin Cidado [États-Unis] ; Brian G. Blair [États-Unis] ; David Chu [États-Unis] ; Timothy Burns [États-Unis] ; Michaela J. Higgins [États-Unis] ; Vered Stearns [États-Unis] ; Lisa Jacobs [États-Unis] ; Mehran Habibi [États-Unis] ; Julie Lange [États-Unis] ; Paula J. Hurley [États-Unis] ; Josh Lauring [États-Unis] ; Dustin Vandenberg [États-Unis] ; Jill Kessler [États-Unis] ; Stacie Jeter [États-Unis] ; Michael L. Samuels [États-Unis] ; Dianna Maar [États-Unis] ; Leslie Cope [États-Unis] ; Ashley Cimino-Mathews [États-Unis] ; Pedram Argani [États-Unis] ; Antonio C. Wolff [États-Unis] ; Ben H. Park [États-Unis]

Source :

Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2014.

RBID : PMC:4024333

Descripteurs français

KwdFr :
- ADN tumoral (), ADN tumoral (génétique), ADN tumoral (sang), Adulte, Adulte d'âge moyen, Analyse de mutations d'ADN (), Exons (génétique), Femelle, Humains, Mutation, Phosphatidylinositol 3-kinases (génétique), Période postopératoire, Période préopératoire, Reproductibilité des résultats, Réaction de polymérisation en chaîne (), Sensibilité et spécificité, Stade de la tumeur, Sujet âgé, Tumeurs du sein (), Tumeurs du sein (diagnostic), Tumeurs du sein (génétique), Études prospectives.
MESH :
- diagnostic : Tumeurs du sein.
- génétique : ADN tumoral, Exons, Phosphatidylinositol 3-kinases, Tumeurs du sein.
- sang : ADN tumoral.
- ADN tumoral, Adulte, Adulte d'âge moyen, Analyse de mutations d'ADN, Femelle, Humains, Mutation, Période postopératoire, Période préopératoire, Reproductibilité des résultats, Réaction de polymérisation en chaîne, Sensibilité et spécificité, Stade de la tumeur, Sujet âgé, Tumeurs du sein, Études prospectives.

English descriptors

KwdEn :
- Adult, Aged, Breast Neoplasms (diagnosis), Breast Neoplasms (genetics), Breast Neoplasms (surgery), DNA Mutational Analysis (methods), DNA, Neoplasm (blood), DNA, Neoplasm (chemistry), DNA, Neoplasm (genetics), Exons (genetics), Female, Humans, Middle Aged, Mutation, Neoplasm Staging, Phosphatidylinositol 3-Kinases (genetics), Polymerase Chain Reaction (methods), Postoperative Period, Preoperative Period, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity.
MESH :
- chemical , blood : DNA, Neoplasm.
- chemical , chemistry : DNA, Neoplasm.
- diagnosis : Breast Neoplasms.
- genetics : Breast Neoplasms, DNA, Neoplasm, Exons, Phosphatidylinositol 3-Kinases.
- methods : DNA Mutational Analysis, Polymerase Chain Reaction.
- surgery : Breast Neoplasms.
- Adult, Aged, Female, Humans, Middle Aged, Mutation, Neoplasm Staging, Postoperative Period, Preoperative Period, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity.

Abstract

Purpose

Detecting circulating plasma tumor DNA (ptDNA) in early stage cancer patients has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.

Experimental Design

In this prospective study, primary breast tumors and matched pre- and post-surgery blood samples were collected from early stage breast cancer patients (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR.

Results

Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Pre-surgery plasma samples (n=29) were then analyzed for PIK3CA mutations using ddPCR. Of the fifteen PIK3CA mutations detected in tumors by ddPCR, fourteen of the corresponding mutations were detected in pre-surgical ptDNA, while no mutations were found in plasma from patients with PIK3CA wild type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation positive ptDNA pre-surgery had ddPCR analysis of post-surgery plasma, with five patients having detectable ptDNA post-surgery.

Conclusions

This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in early stage breast cancer patients. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024333

DOI: 10.1158/1078-0432.CCR-13-2933
PubMed: 24504125
PubMed Central: 4024333

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Sasidharan Balukrishna

<affiliation><nlm:aff id="A2">Christian Medical College Vellore, Tamil Nadu, India 632004</nlm:aff>
<wicri:noCountry code="subfield">India 632004</wicri:noCountry>
</affiliation>

Le document en format XML

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<author><name sortKey="Lange, Julie" sort="Lange, Julie" uniqKey="Lange J" first="Julie" last="Lange">Julie Lange</name>
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<author><name sortKey="Lauring, Josh" sort="Lauring, Josh" uniqKey="Lauring J" first="Josh" last="Lauring">Josh Lauring</name>
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<author><name sortKey="Kessler, Jill" sort="Kessler, Jill" uniqKey="Kessler J" first="Jill" last="Kessler">Jill Kessler</name>
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<author><name sortKey="Jeter, Stacie" sort="Jeter, Stacie" uniqKey="Jeter S" first="Stacie" last="Jeter">Stacie Jeter</name>
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<author><name sortKey="Samuels, Michael L" sort="Samuels, Michael L" uniqKey="Samuels M" first="Michael L." last="Samuels">Michael L. Samuels</name>
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<author><name sortKey="Maar, Dianna" sort="Maar, Dianna" uniqKey="Maar D" first="Dianna" last="Maar">Dianna Maar</name>
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<author><name sortKey="Cope, Leslie" sort="Cope, Leslie" uniqKey="Cope L" first="Leslie" last="Cope">Leslie Cope</name>
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<author><name sortKey="Cimino Mathews, Ashley" sort="Cimino Mathews, Ashley" uniqKey="Cimino Mathews A" first="Ashley" last="Cimino-Mathews">Ashley Cimino-Mathews</name>
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<author><name sortKey="Argani, Pedram" sort="Argani, Pedram" uniqKey="Argani P" first="Pedram" last="Argani">Pedram Argani</name>
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<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
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<author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
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<author><name sortKey="Park, Ben H" sort="Park, Ben H" uniqKey="Park B" first="Ben H." last="Park">Ben H. Park</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Detection of Cancer DNA in Plasma of Early Stage Breast Cancer Patients</title>
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<author><name sortKey="Jelovac, Danijela" sort="Jelovac, Danijela" uniqKey="Jelovac D" first="Danijela" last="Jelovac">Danijela Jelovac</name>
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<author><name sortKey="Balukrishna, Sasidharan" sort="Balukrishna, Sasidharan" uniqKey="Balukrishna S" first="Sasidharan" last="Balukrishna">Sasidharan Balukrishna</name>
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<wicri:noCountry code="subfield">India 632004</wicri:noCountry>
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</author>
<author><name sortKey="Cochran, Rory" sort="Cochran, Rory" uniqKey="Cochran R" first="Rory" last="Cochran">Rory Cochran</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Croessmann, Sarah" sort="Croessmann, Sarah" uniqKey="Croessmann S" first="Sarah" last="Croessmann">Sarah Croessmann</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zabransky, Daniel J" sort="Zabransky, Daniel J" uniqKey="Zabransky D" first="Daniel J." last="Zabransky">Daniel J. Zabransky</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wong, Hong Yuen" sort="Wong, Hong Yuen" uniqKey="Wong H" first="Hong Yuen" last="Wong">Hong Yuen Wong</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Toro, Patricia Valda" sort="Toro, Patricia Valda" uniqKey="Toro P" first="Patricia Valda" last="Toro">Patricia Valda Toro</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cidado, Justin" sort="Cidado, Justin" uniqKey="Cidado J" first="Justin" last="Cidado">Justin Cidado</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Blair, Brian G" sort="Blair, Brian G" uniqKey="Blair B" first="Brian G." last="Blair">Brian G. Blair</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chu, David" sort="Chu, David" uniqKey="Chu D" first="David" last="Chu">David Chu</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Burns, Timothy" sort="Burns, Timothy" uniqKey="Burns T" first="Timothy" last="Burns">Timothy Burns</name>
<affiliation wicri:level="2"><nlm:aff id="A3">University of Pittsburgh Hillman Cancer Center, Pittsburgh, PA 15213-1863</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>University of Pittsburgh Hillman Cancer Center, Pittsburgh</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Higgins, Michaela J" sort="Higgins, Michaela J" uniqKey="Higgins M" first="Michaela J." last="Higgins">Michaela J. Higgins</name>
<affiliation wicri:level="2"><nlm:aff id="A4">Massachusetts General Hospital, Boston, MA 02114-2696</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Massachusetts General Hospital, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jacobs, Lisa" sort="Jacobs, Lisa" uniqKey="Jacobs L" first="Lisa" last="Jacobs">Lisa Jacobs</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Habibi, Mehran" sort="Habibi, Mehran" uniqKey="Habibi M" first="Mehran" last="Habibi">Mehran Habibi</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lange, Julie" sort="Lange, Julie" uniqKey="Lange J" first="Julie" last="Lange">Julie Lange</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hurley, Paula J" sort="Hurley, Paula J" uniqKey="Hurley P" first="Paula J." last="Hurley">Paula J. Hurley</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lauring, Josh" sort="Lauring, Josh" uniqKey="Lauring J" first="Josh" last="Lauring">Josh Lauring</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Vandenberg, Dustin" sort="Vandenberg, Dustin" uniqKey="Vandenberg D" first="Dustin" last="Vandenberg">Dustin Vandenberg</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kessler, Jill" sort="Kessler, Jill" uniqKey="Kessler J" first="Jill" last="Kessler">Jill Kessler</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jeter, Stacie" sort="Jeter, Stacie" uniqKey="Jeter S" first="Stacie" last="Jeter">Stacie Jeter</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Samuels, Michael L" sort="Samuels, Michael L" uniqKey="Samuels M" first="Michael L." last="Samuels">Michael L. Samuels</name>
<affiliation wicri:level="2"><nlm:aff id="A5">RainDance Technologies, Billerica, MA 01821</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>RainDance Technologies, Billerica</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maar, Dianna" sort="Maar, Dianna" uniqKey="Maar D" first="Dianna" last="Maar">Dianna Maar</name>
<affiliation wicri:level="2"><nlm:aff id="A6">Bio-Rad Laboratories, Digital Biology Center, Pleasanton, CA 94566</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Bio-Rad Laboratories, Digital Biology Center, Pleasanton</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cope, Leslie" sort="Cope, Leslie" uniqKey="Cope L" first="Leslie" last="Cope">Leslie Cope</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cimino Mathews, Ashley" sort="Cimino Mathews, Ashley" uniqKey="Cimino Mathews A" first="Ashley" last="Cimino-Mathews">Ashley Cimino-Mathews</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Argani, Pedram" sort="Argani, Pedram" uniqKey="Argani P" first="Pedram" last="Argani">Pedram Argani</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Park, Ben H" sort="Park, Ben H" uniqKey="Park B" first="Ben H." last="Park">Ben H. Park</name>
<affiliation wicri:level="2"><nlm:aff id="A1">The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title>
<idno type="ISSN">1078-0432</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Breast Neoplasms (diagnosis)</term>
<term>Breast Neoplasms (genetics)</term>
<term>Breast Neoplasms (surgery)</term>
<term>DNA Mutational Analysis (methods)</term>
<term>DNA, Neoplasm (blood)</term>
<term>DNA, Neoplasm (chemistry)</term>
<term>DNA, Neoplasm (genetics)</term>
<term>Exons (genetics)</term>
<term>Female</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Neoplasm Staging</term>
<term>Phosphatidylinositol 3-Kinases (genetics)</term>
<term>Polymerase Chain Reaction (methods)</term>
<term>Postoperative Period</term>
<term>Preoperative Period</term>
<term>Prospective Studies</term>
<term>Reproducibility of Results</term>
<term>Sensitivity and Specificity</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN tumoral ()</term>
<term>ADN tumoral (génétique)</term>
<term>ADN tumoral (sang)</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN ()</term>
<term>Exons (génétique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutation</term>
<term>Phosphatidylinositol 3-kinases (génétique)</term>
<term>Période postopératoire</term>
<term>Période préopératoire</term>
<term>Reproductibilité des résultats</term>
<term>Réaction de polymérisation en chaîne ()</term>
<term>Sensibilité et spécificité</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Tumeurs du sein ()</term>
<term>Tumeurs du sein (diagnostic)</term>
<term>Tumeurs du sein (génétique)</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>DNA, Neoplasm</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA, Neoplasm</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Breast Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term>
<term>DNA, Neoplasm</term>
<term>Exons</term>
<term>Phosphatidylinositol 3-Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN tumoral</term>
<term>Exons</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>DNA Mutational Analysis</term>
<term>Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ADN tumoral</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Breast Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Female</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Neoplasm Staging</term>
<term>Postoperative Period</term>
<term>Preoperative Period</term>
<term>Prospective Studies</term>
<term>Reproducibility of Results</term>
<term>Sensitivity and Specificity</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>ADN tumoral</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutation</term>
<term>Période postopératoire</term>
<term>Période préopératoire</term>
<term>Reproductibilité des résultats</term>
<term>Réaction de polymérisation en chaîne</term>
<term>Sensibilité et spécificité</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Tumeurs du sein</term>
<term>Études prospectives</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title>
<p id="P1">Detecting circulating plasma tumor DNA (ptDNA) in early stage cancer patients has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.</p>
</sec>
<sec id="S2"><title>Experimental Design</title>
<p id="P2">In this prospective study, primary breast tumors and matched pre- and post-surgery blood samples were collected from early stage breast cancer patients (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common <italic>PIK3CA</italic>
 mutations, and DNA from these tumors and matched plasma were then analyzed for <italic>PIK3CA</italic>
 mutations using ddPCR.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Sequencing of tumors identified seven <italic>PIK3CA</italic>
 exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Pre-surgery plasma samples (n=29) were then analyzed for <italic>PIK3CA</italic>
 mutations using ddPCR. Of the fifteen <italic>PIK3CA</italic>
 mutations detected in tumors by ddPCR, fourteen of the corresponding mutations were detected in pre-surgical ptDNA, while no mutations were found in plasma from patients with <italic>PIK3CA</italic>
 wild type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation positive ptDNA pre-surgery had ddPCR analysis of post-surgery plasma, with five patients having detectable ptDNA post-surgery.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in early stage breast cancer patients. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.</p>
</sec>
</div>
</front>
</TEI>
</record>

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Detection of Cancer DNA in Plasma of Early Stage Breast Cancer Patients

Detection of Cancer DNA in Plasma of Early Stage Breast Cancer Patients

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