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Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy.

Identifieur interne : 001D28 ( Main/Exploration ); précédent : 001D27; suivant : 001D29

Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy.

Auteurs : Kathrin Strasser-Weippl [Autriche] ; Nora Horick [États-Unis] ; Ian E. Smith [Royaume-Uni] ; Joyce O'Shaughnessy [États-Unis] ; Bent Ejlertsen [Danemark] ; Frances Boyle [Australie] ; Aman U. Buzdar [États-Unis] ; Pierre Fumoleau [France] ; William Gradishar [États-Unis] ; Miguel Martin [Espagne] ; Beverly Moy [États-Unis] ; Martine Piccart-Gebhart [Belgique] ; Kathleen I. Pritchard [Canada] ; Deborah Lindquist [États-Unis] ; Erica Rappold [États-Unis] ; Dianne M. Finkelstein [États-Unis] ; Paul E. Goss [États-Unis]

Source :

RBID : pubmed:26829011

Descripteurs français

English descriptors

Abstract

In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib ≤1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials.

DOI: 10.1016/j.ejca.2015.12.024
PubMed: 26829011


Affiliations:


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Le document en format XML

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<name sortKey="Buzdar, Aman U" sort="Buzdar, Aman U" uniqKey="Buzdar A" first="Aman U" last="Buzdar">Aman U. Buzdar</name>
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<nlm:affiliation>University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: abuzdar@mdanderson.org.</nlm:affiliation>
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<name sortKey="Fumoleau, Pierre" sort="Fumoleau, Pierre" uniqKey="Fumoleau P" first="Pierre" last="Fumoleau">Pierre Fumoleau</name>
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<name sortKey="Gradishar, William" sort="Gradishar, William" uniqKey="Gradishar W" first="William" last="Gradishar">William Gradishar</name>
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<name sortKey="Martin, Miguel" sort="Martin, Miguel" uniqKey="Martin M" first="Miguel" last="Martin">Miguel Martin</name>
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<wicri:regionArea>Arizona Oncology, US Oncology, Sedona, AZ</wicri:regionArea>
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<name sortKey="Rappold, Erica" sort="Rappold, Erica" uniqKey="Rappold E" first="Erica" last="Rappold">Erica Rappold</name>
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<name sortKey="Finkelstein, Dianne M" sort="Finkelstein, Dianne M" uniqKey="Finkelstein D" first="Dianne M" last="Finkelstein">Dianne M. Finkelstein</name>
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<title xml:lang="en">Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy.</title>
<author>
<name sortKey="Strasser Weippl, Kathrin" sort="Strasser Weippl, Kathrin" uniqKey="Strasser Weippl K" first="Kathrin" last="Strasser-Weippl">Kathrin Strasser-Weippl</name>
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<nlm:affiliation>Center for Oncology and Hematology, Wilhelminen Hospital, Vienna, Austria. Electronic address: kathrin.strasserweippl@gmail.com.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Center for Oncology and Hematology, Wilhelminen Hospital, Vienna</wicri:regionArea>
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<settlement type="city">Vienne (Autriche)</settlement>
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<name sortKey="Horick, Nora" sort="Horick, Nora" uniqKey="Horick N" first="Nora" last="Horick">Nora Horick</name>
<affiliation wicri:level="2">
<nlm:affiliation>Massachusetts General Hospital Biostatistics Center, Boston, MA, USA. Electronic address: nhorick@partners.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Massachusetts General Hospital Biostatistics Center, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<name sortKey="Smith, Ian E" sort="Smith, Ian E" uniqKey="Smith I" first="Ian E" last="Smith">Ian E. Smith</name>
<affiliation wicri:level="3">
<nlm:affiliation>Royal Marsden Hospital, London, UK. Electronic address: ian.smith@rmh.nhs.uk.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Marsden Hospital, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
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<name sortKey="O Shaughnessy, Joyce" sort="O Shaughnessy, Joyce" uniqKey="O Shaughnessy J" first="Joyce" last="O'Shaughnessy">Joyce O'Shaughnessy</name>
<affiliation wicri:level="2">
<nlm:affiliation>Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA. Electronic address: Joyce.OShaughnessy@usoncology.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
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<name sortKey="Ejlertsen, Bent" sort="Ejlertsen, Bent" uniqKey="Ejlertsen B" first="Bent" last="Ejlertsen">Bent Ejlertsen</name>
<affiliation wicri:level="3">
<nlm:affiliation>Rigshospitalet, DBCG Secretariat, Copenhagen, Denmark. Electronic address: ejlertsen@dadlnet.dk.</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Rigshospitalet, DBCG Secretariat, Copenhagen</wicri:regionArea>
<placeName>
<settlement type="city">Copenhague</settlement>
<region type="région" nuts="2">Hovedstaden</region>
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<name sortKey="Boyle, Frances" sort="Boyle, Frances" uniqKey="Boyle F" first="Frances" last="Boyle">Frances Boyle</name>
<affiliation wicri:level="1">
<nlm:affiliation>Mater Hospital, North Sydney, NSW, Australia. Electronic address: franb@bigpond.net.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Mater Hospital, North Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
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<name sortKey="Buzdar, Aman U" sort="Buzdar, Aman U" uniqKey="Buzdar A" first="Aman U" last="Buzdar">Aman U. Buzdar</name>
<affiliation wicri:level="2">
<nlm:affiliation>University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: abuzdar@mdanderson.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Texas MD Anderson Cancer Center, Houston, TX</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Fumoleau, Pierre" sort="Fumoleau, Pierre" uniqKey="Fumoleau P" first="Pierre" last="Fumoleau">Pierre Fumoleau</name>
<affiliation wicri:level="3">
<nlm:affiliation>Centre GF Leclerc, Dijon, France. Electronic address: pfumoleau@cgfl.fr.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre GF Leclerc, Dijon</wicri:regionArea>
<placeName>
<region type="region">Bourgogne-Franche-Comté</region>
<region type="old region">Bourgogne</region>
<settlement type="city">Dijon</settlement>
</placeName>
</affiliation>
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<name sortKey="Gradishar, William" sort="Gradishar, William" uniqKey="Gradishar W" first="William" last="Gradishar">William Gradishar</name>
<affiliation wicri:level="2">
<nlm:affiliation>Northwestern University, Chicago, IL, USA. Electronic address: WGradishar@nmff.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Northwestern University, Chicago, IL</wicri:regionArea>
<placeName>
<region type="state">Illinois</region>
</placeName>
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<name sortKey="Martin, Miguel" sort="Martin, Miguel" uniqKey="Martin M" first="Miguel" last="Martin">Miguel Martin</name>
<affiliation wicri:level="3">
<nlm:affiliation>Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. Electronic address: mmartin@geicam.org.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
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<name sortKey="Moy, Beverly" sort="Moy, Beverly" uniqKey="Moy B" first="Beverly" last="Moy">Beverly Moy</name>
<affiliation wicri:level="2">
<nlm:affiliation>Massachusetts General Hospital, Boston, MA, USA. Electronic address: bmoy@partners.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Massachusetts General Hospital, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
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<name sortKey="Piccart Gebhart, Martine" sort="Piccart Gebhart, Martine" uniqKey="Piccart Gebhart M" first="Martine" last="Piccart-Gebhart">Martine Piccart-Gebhart</name>
<affiliation wicri:level="4">
<nlm:affiliation>Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Institut Jules Bordet, Université Libre de Bruxelles, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
<settlement type="city">Bruxelles</settlement>
</placeName>
<orgName type="university">Université libre de Bruxelles</orgName>
</affiliation>
</author>
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<name sortKey="Pritchard, Kathleen I" sort="Pritchard, Kathleen I" uniqKey="Pritchard K" first="Kathleen I" last="Pritchard">Kathleen I. Pritchard</name>
<affiliation wicri:level="4">
<nlm:affiliation>Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address: kathy.pritchard@sunnybrook.ca.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Lindquist, Deborah" sort="Lindquist, Deborah" uniqKey="Lindquist D" first="Deborah" last="Lindquist">Deborah Lindquist</name>
<affiliation wicri:level="2">
<nlm:affiliation>Arizona Oncology, US Oncology, Sedona, AZ, USA. Electronic address: deborah.lindquist@usoncology.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Arizona Oncology, US Oncology, Sedona, AZ</wicri:regionArea>
<placeName>
<region type="state">Arizona</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rappold, Erica" sort="Rappold, Erica" uniqKey="Rappold E" first="Erica" last="Rappold">Erica Rappold</name>
<affiliation wicri:level="2">
<nlm:affiliation>GlaxoSmithKline, Collegeville, PA, USA. Electronic address: mprcer@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>GlaxoSmithKline, Collegeville, PA</wicri:regionArea>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Finkelstein, Dianne M" sort="Finkelstein, Dianne M" uniqKey="Finkelstein D" first="Dianne M" last="Finkelstein">Dianne M. Finkelstein</name>
<affiliation wicri:level="2">
<nlm:affiliation>Massachusetts General Hospital Biostatistics Center, Boston, MA, USA. Electronic address: dfinkelstein@partners.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Massachusetts General Hospital Biostatistics Center, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Goss, Paul E" sort="Goss, Paul E" uniqKey="Goss P" first="Paul E" last="Goss">Paul E. Goss</name>
<affiliation wicri:level="2">
<nlm:affiliation>Massachusetts General Hospital, Boston, MA, USA. Electronic address: pgoss@partners.org.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Massachusetts General Hospital, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
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</author>
</analytic>
<series>
<title level="j">European journal of cancer (Oxford, England : 1990)</title>
<idno type="eISSN">1879-0852</idno>
<imprint>
<date when="2016" type="published">2016</date>
</imprint>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antineoplastic Agents (adverse effects)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Breast Neoplasms (drug therapy)</term>
<term>Breast Neoplasms (enzymology)</term>
<term>Breast Neoplasms (genetics)</term>
<term>Breast Neoplasms (mortality)</term>
<term>Breast Neoplasms (pathology)</term>
<term>Chemotherapy, Adjuvant</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Humans</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Kaplan-Meier Estimate</term>
<term>Middle Aged</term>
<term>Neoplasm Recurrence, Local</term>
<term>Neoplasm Staging</term>
<term>Patient Selection</term>
<term>Precision Medicine</term>
<term>Proportional Hazards Models</term>
<term>Protein Kinase Inhibitors (adverse effects)</term>
<term>Protein Kinase Inhibitors (therapeutic use)</term>
<term>Quinazolines (adverse effects)</term>
<term>Quinazolines (therapeutic use)</term>
<term>Receptor, ErbB-2 (antagonists & inhibitors)</term>
<term>Receptor, ErbB-2 (genetics)</term>
<term>Receptor, ErbB-2 (metabolism)</term>
<term>Signal Transduction (drug effects)</term>
<term>Time Factors</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Antinéoplasiques (effets indésirables)</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Estimation de Kaplan-Meier</term>
<term>Facteurs temps</term>
<term>Femelle</term>
<term>Humains</term>
<term>Inhibiteurs de protéines kinases (effets indésirables)</term>
<term>Inhibiteurs de protéines kinases (usage thérapeutique)</term>
<term>Modèles de hasards proportionnels</term>
<term>Médecine individualisée</term>
<term>Quinazolines (effets indésirables)</term>
<term>Quinazolines (usage thérapeutique)</term>
<term>Récepteur ErbB-2 (antagonistes et inhibiteurs)</term>
<term>Récepteur ErbB-2 (génétique)</term>
<term>Récepteur ErbB-2 (métabolisme)</term>
<term>Récidive tumorale locale</term>
<term>Résultat thérapeutique</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Sélection de patients</term>
<term>Technique FISH</term>
<term>Traitement médicamenteux adjuvant</term>
<term>Transduction du signal ()</term>
<term>Tumeurs du sein (anatomopathologie)</term>
<term>Tumeurs du sein (enzymologie)</term>
<term>Tumeurs du sein (génétique)</term>
<term>Tumeurs du sein (mortalité)</term>
<term>Tumeurs du sein (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en">
<term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Receptor, ErbB-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Receptor, ErbB-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Receptor, ErbB-2</term>
</keywords>
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<term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
<term>Quinazolines</term>
</keywords>
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<term>Tumeurs du sein</term>
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<term>Récepteur ErbB-2</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Signal Transduction</term>
</keywords>
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<term>Breast Neoplasms</term>
</keywords>
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<term>Antinéoplasiques</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Quinazolines</term>
</keywords>
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<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>Breast Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Breast Neoplasms</term>
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<term>Tumeurs du sein</term>
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<term>Breast Neoplasms</term>
</keywords>
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<term>Tumeurs du sein</term>
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<term>Récepteur ErbB-2</term>
</keywords>
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<term>Breast Neoplasms</term>
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<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Antinéoplasiques</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Chemotherapy, Adjuvant</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Humans</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Kaplan-Meier Estimate</term>
<term>Middle Aged</term>
<term>Neoplasm Recurrence, Local</term>
<term>Neoplasm Staging</term>
<term>Patient Selection</term>
<term>Precision Medicine</term>
<term>Proportional Hazards Models</term>
<term>Time Factors</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Estimation de Kaplan-Meier</term>
<term>Facteurs temps</term>
<term>Femelle</term>
<term>Humains</term>
<term>Modèles de hasards proportionnels</term>
<term>Médecine individualisée</term>
<term>Récidive tumorale locale</term>
<term>Résultat thérapeutique</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Sélection de patients</term>
<term>Technique FISH</term>
<term>Traitement médicamenteux adjuvant</term>
<term>Transduction du signal</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib ≤1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Autriche</li>
<li>Belgique</li>
<li>Canada</li>
<li>Danemark</li>
<li>Espagne</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Arizona</li>
<li>Bourgogne</li>
<li>Bourgogne-Franche-Comté</li>
<li>Communauté de Madrid</li>
<li>Grand Londres</li>
<li>Hovedstaden</li>
<li>Illinois</li>
<li>Massachusetts</li>
<li>Ontario</li>
<li>Pennsylvanie</li>
<li>Région de Bruxelles-Capitale</li>
<li>Texas</li>
<li>Vienne (Autriche)</li>
</region>
<settlement>
<li>Bruxelles</li>
<li>Copenhague</li>
<li>Dijon</li>
<li>Londres</li>
<li>Madrid</li>
<li>Toronto</li>
<li>Vienne (Autriche)</li>
</settlement>
<orgName>
<li>Université de Toronto</li>
<li>Université libre de Bruxelles</li>
</orgName>
</list>
<tree>
<country name="Autriche">
<region name="Vienne (Autriche)">
<name sortKey="Strasser Weippl, Kathrin" sort="Strasser Weippl, Kathrin" uniqKey="Strasser Weippl K" first="Kathrin" last="Strasser-Weippl">Kathrin Strasser-Weippl</name>
</region>
</country>
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<region name="Massachusetts">
<name sortKey="Horick, Nora" sort="Horick, Nora" uniqKey="Horick N" first="Nora" last="Horick">Nora Horick</name>
</region>
<name sortKey="Buzdar, Aman U" sort="Buzdar, Aman U" uniqKey="Buzdar A" first="Aman U" last="Buzdar">Aman U. Buzdar</name>
<name sortKey="Finkelstein, Dianne M" sort="Finkelstein, Dianne M" uniqKey="Finkelstein D" first="Dianne M" last="Finkelstein">Dianne M. Finkelstein</name>
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<name sortKey="Gradishar, William" sort="Gradishar, William" uniqKey="Gradishar W" first="William" last="Gradishar">William Gradishar</name>
<name sortKey="Lindquist, Deborah" sort="Lindquist, Deborah" uniqKey="Lindquist D" first="Deborah" last="Lindquist">Deborah Lindquist</name>
<name sortKey="Moy, Beverly" sort="Moy, Beverly" uniqKey="Moy B" first="Beverly" last="Moy">Beverly Moy</name>
<name sortKey="O Shaughnessy, Joyce" sort="O Shaughnessy, Joyce" uniqKey="O Shaughnessy J" first="Joyce" last="O'Shaughnessy">Joyce O'Shaughnessy</name>
<name sortKey="Rappold, Erica" sort="Rappold, Erica" uniqKey="Rappold E" first="Erica" last="Rappold">Erica Rappold</name>
</country>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Smith, Ian E" sort="Smith, Ian E" uniqKey="Smith I" first="Ian E" last="Smith">Ian E. Smith</name>
</region>
</country>
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<region name="Hovedstaden">
<name sortKey="Ejlertsen, Bent" sort="Ejlertsen, Bent" uniqKey="Ejlertsen B" first="Bent" last="Ejlertsen">Bent Ejlertsen</name>
</region>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Boyle, Frances" sort="Boyle, Frances" uniqKey="Boyle F" first="Frances" last="Boyle">Frances Boyle</name>
</noRegion>
</country>
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<region name="Bourgogne-Franche-Comté">
<name sortKey="Fumoleau, Pierre" sort="Fumoleau, Pierre" uniqKey="Fumoleau P" first="Pierre" last="Fumoleau">Pierre Fumoleau</name>
</region>
</country>
<country name="Espagne">
<region name="Communauté de Madrid">
<name sortKey="Martin, Miguel" sort="Martin, Miguel" uniqKey="Martin M" first="Miguel" last="Martin">Miguel Martin</name>
</region>
</country>
<country name="Belgique">
<region name="Région de Bruxelles-Capitale">
<name sortKey="Piccart Gebhart, Martine" sort="Piccart Gebhart, Martine" uniqKey="Piccart Gebhart M" first="Martine" last="Piccart-Gebhart">Martine Piccart-Gebhart</name>
</region>
</country>
<country name="Canada">
<region name="Ontario">
<name sortKey="Pritchard, Kathleen I" sort="Pritchard, Kathleen I" uniqKey="Pritchard K" first="Kathleen I" last="Pritchard">Kathleen I. Pritchard</name>
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