Precision medicine for metastatic breast cancer--limitations and solutions.
Identifieur interne : 002985 ( Main/Exploration ); précédent : 002984; suivant : 002986Precision medicine for metastatic breast cancer--limitations and solutions.
Auteurs : Monica Arnedos [France] ; Cecile Vicier [France] ; Sherene Loi [Australie] ; Celine Lefebvre [France] ; Stefan Michiels [France] ; Herve Bonnefoi [France] ; Fabrice Andre [France]Source :
- Nature reviews. Clinical oncology [ 1759-4782 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- anatomopathologie : Tumeurs du sein.
- génétique : Tumeurs du sein.
- tendances : Génomique.
- traitement médicamenteux : Tumeurs du sein.
- Femelle, Humains, Médecine individualisée, Métastase tumorale.
English descriptors
- KwdEn :
- MESH :
- drug therapy : Breast Neoplasms.
- genetics : Breast Neoplasms.
- pathology : Breast Neoplasms.
- trends : Genomics.
- Female, Humans, Neoplasm Metastasis, Precision Medicine.
Abstract
The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The identification of driver mutational events remains the biggest challenge, because, with the few exceptions of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer exist. The development of bioinformatic tools to help identify driver mutations, together with assessment of pathway activation and dependency should help resolve this issue in the future. The occurrence of secondary resistance, such as ESR1 mutations, following endocrine therapy poses a further challenge. Ultra-deep sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early detection of the genetic events underlying resistance and inform on combination therapy approaches. Beside these scientific challenges, logistical and operational issues are a major limitation to the development of precision medicine. For example, the low incidence of most candidate genomic alterations hinders randomized trials, as the number of patients to be screened would be too high. We discuss these limitations and the solutions, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.
DOI: 10.1038/nrclinonc.2015.123
PubMed: 26196250
Affiliations:
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Centre, University of Melbourne, East Melbourne, VIC 3002, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC 3002</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lefebvre, Celine" sort="Lefebvre, Celine" uniqKey="Lefebvre C" first="Celine" last="Lefebvre">Celine Lefebvre</name><affiliation wicri:level="1"><nlm:affiliation>INSERM Unit U981, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unit U981, Gustave Roussy and Université Paris Sud, 94800 Villejuif</wicri:regionArea><wicri:noRegion>94800 Villejuif</wicri:noRegion><wicri:noRegion>94800 Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biostatistics and Epidemiology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Biostatistics and Epidemiology, Gustave Roussy and Université Paris Sud, 94800 Villejuif</wicri:regionArea><wicri:noRegion>94800 Villejuif</wicri:noRegion><wicri:noRegion>94800 Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Bonnefoi, Herve" sort="Bonnefoi, Herve" uniqKey="Bonnefoi H" first="Herve" last="Bonnefoi">Herve Bonnefoi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology and INSERM U916, Institut Bergonié, 229 Cours de l'Argonne, 33000, Bordeaux, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology and INSERM U916, Institut Bergonié, 229 Cours de l'Argonne, 33000, Bordeaux</wicri:regionArea><wicri:noRegion>33000, Bordeaux</wicri:noRegion><wicri:noRegion>33000, Bordeaux</wicri:noRegion></affiliation></author><author><name sortKey="Andre, Fabrice" sort="Andre, Fabrice" uniqKey="Andre F" first="Fabrice" last="Andre">Fabrice Andre</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, Gustave Roussy and Université Paris Sud, 94800 Villejuif</wicri:regionArea><wicri:noRegion>94800 Villejuif</wicri:noRegion><wicri:noRegion>94800 Villejuif</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature reviews. Clinical oncology</title><idno type="eISSN">1759-4782</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Breast Neoplasms (drug therapy)</term><term>Breast Neoplasms (genetics)</term><term>Breast Neoplasms (pathology)</term><term>Female</term><term>Genomics (trends)</term><term>Humans</term><term>Neoplasm Metastasis</term><term>Precision Medicine</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Femelle</term><term>Génomique (tendances)</term><term>Humains</term><term>Médecine individualisée</term><term>Métastase tumorale</term><term>Tumeurs du sein (anatomopathologie)</term><term>Tumeurs du sein (génétique)</term><term>Tumeurs du sein (traitement médicamenteux)</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="tendances" xml:lang="fr"><term>Génomique</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="trends" xml:lang="en"><term>Genomics</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Female</term><term>Humans</term><term>Neoplasm Metastasis</term><term>Precision Medicine</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Femelle</term><term>Humains</term><term>Médecine individualisée</term><term>Métastase tumorale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The identification of driver mutational events remains the biggest challenge, because, with the few exceptions of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer exist. The development of bioinformatic tools to help identify driver mutations, together with assessment of pathway activation and dependency should help resolve this issue in the future. The occurrence of secondary resistance, such as ESR1 mutations, following endocrine therapy poses a further challenge. Ultra-deep sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early detection of the genetic events underlying resistance and inform on combination therapy approaches. Beside these scientific challenges, logistical and operational issues are a major limitation to the development of precision medicine. For example, the low incidence of most candidate genomic alterations hinders randomized trials, as the number of patients to be screened would be too high. We discuss these limitations and the solutions, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Melbourne</li><li>Villejuif</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Arnedos, Monica" sort="Arnedos, Monica" uniqKey="Arnedos M" first="Monica" last="Arnedos">Monica Arnedos</name></region><name sortKey="Andre, Fabrice" sort="Andre, Fabrice" uniqKey="Andre F" first="Fabrice" last="Andre">Fabrice Andre</name><name sortKey="Bonnefoi, Herve" sort="Bonnefoi, Herve" uniqKey="Bonnefoi H" first="Herve" last="Bonnefoi">Herve Bonnefoi</name><name sortKey="Lefebvre, Celine" sort="Lefebvre, Celine" uniqKey="Lefebvre C" first="Celine" last="Lefebvre">Celine Lefebvre</name><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name><name sortKey="Vicier, Cecile" sort="Vicier, Cecile" uniqKey="Vicier C" first="Cecile" last="Vicier">Cecile Vicier</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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