Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab
Identifieur interne : 002678 ( Main/Exploration ); précédent : 002677; suivant : 002679Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab
Auteurs : Roberto Salgado ; Carsten Denkert ; Christine Campbell ; Peter Savas ; Paolo Nuciforo ; Claudia Aura ; Evandro De Azambuja ; Holger Eidtmann ; Catherine E. Ellis ; Jose Baselga ; Martine J. Piccart-Gebhart ; Stefan Michiels ; Ian Bradbury ; Christos Sotiriou ; Sherene LoiSource :
- JAMA oncology [ 2374-2437 ] ; 2015.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Antinéoplasiques (effets indésirables), Antinéoplasiques (usage thérapeutique), Facteurs de risque, Facteurs temps, Femelle, Humains, Induction de rémission, Inhibiteurs de protéines kinases (effets indésirables), Inhibiteurs de protéines kinases (usage thérapeutique), Jeune adulte, Lymphocytes TIL (), Lymphocytes TIL (immunologie), Marqueurs biologiques tumoraux (antagonistes et inhibiteurs), Marqueurs biologiques tumoraux (métabolisme), Modèles de hasards proportionnels, Odds ratio, Protocoles de polychimiothérapie antinéoplasique (effets indésirables), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Quinazolines (effets indésirables), Quinazolines (usage thérapeutique), Récepteur ErbB-2 (antagonistes et inhibiteurs), Récepteur ErbB-2 (métabolisme), Résultat thérapeutique, Stade de la tumeur, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie sans rechute, Traitement néoadjuvant, Trastuzumab (effets indésirables), Trastuzumab (usage thérapeutique), Tumeurs du sein (anatomopathologie), Tumeurs du sein (enzymologie), Tumeurs du sein (immunologie), Tumeurs du sein (mortalité), Tumeurs du sein (traitement médicamenteux), Études prospectives, Études rétrospectives.
- MESH :
- anatomopathologie : Tumeurs du sein.
- antagonistes et inhibiteurs : Marqueurs biologiques tumoraux, Récepteur ErbB-2.
- effets indésirables : Antinéoplasiques, Inhibiteurs de protéines kinases, Protocoles de polychimiothérapie antinéoplasique, Quinazolines, Trastuzumab.
- enzymologie : Tumeurs du sein.
- immunologie : Lymphocytes TIL, Tumeurs du sein.
- mortalité : Tumeurs du sein.
- métabolisme : Marqueurs biologiques tumoraux, Récepteur ErbB-2.
- traitement médicamenteux : Tumeurs du sein.
- usage thérapeutique : Antinéoplasiques, Inhibiteurs de protéines kinases, Protocoles de polychimiothérapie antinéoplasique, Quinazolines, Trastuzumab.
- Adulte, Adulte d'âge moyen, Facteurs de risque, Facteurs temps, Femelle, Humains, Induction de rémission, Jeune adulte, Lymphocytes TIL, Modèles de hasards proportionnels, Odds ratio, Résultat thérapeutique, Stade de la tumeur, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie sans rechute, Traitement néoadjuvant, Études prospectives, Études rétrospectives.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents (adverse effects), Antineoplastic Agents (therapeutic use), Antineoplastic Combined Chemotherapy Protocols (adverse effects), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Biomarkers, Tumor (antagonists & inhibitors), Biomarkers, Tumor (metabolism), Breast Neoplasms (drug therapy), Breast Neoplasms (enzymology), Breast Neoplasms (immunology), Breast Neoplasms (mortality), Breast Neoplasms (pathology), Disease-Free Survival, Female, Humans, Lymphocytes, Tumor-Infiltrating (drug effects), Lymphocytes, Tumor-Infiltrating (immunology), Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Odds Ratio, Proportional Hazards Models, Prospective Studies, Protein Kinase Inhibitors (adverse effects), Protein Kinase Inhibitors (therapeutic use), Quinazolines (adverse effects), Quinazolines (therapeutic use), Receptor, ErbB-2 (antagonists & inhibitors), Receptor, ErbB-2 (metabolism), Remission Induction, Retrospective Studies, Risk Factors, Time Factors, Trastuzumab (adverse effects), Trastuzumab (therapeutic use), Treatment Outcome, Young Adult.
- MESH :
- chemical , adverse effects : Antineoplastic Agents, Protein Kinase Inhibitors, Quinazolines, Trastuzumab.
- chemical , antagonists & inhibitors : Biomarkers, Tumor, Receptor, ErbB-2.
- chemical , metabolism : Biomarkers, Tumor, Receptor, ErbB-2.
- chemical , therapeutic use : Antineoplastic Agents, Protein Kinase Inhibitors, Quinazolines, Trastuzumab.
- adverse effects : Antineoplastic Combined Chemotherapy Protocols.
- drug effects : Lymphocytes, Tumor-Infiltrating.
- drug therapy : Breast Neoplasms.
- enzymology : Breast Neoplasms.
- immunology : Breast Neoplasms, Lymphocytes, Tumor-Infiltrating.
- mortality : Breast Neoplasms.
- pathology : Breast Neoplasms.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Odds Ratio, Proportional Hazards Models, Prospective Studies, Remission Induction, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Young Adult.
Abstract
The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with adjuvant trastuzumab and chemotherapy. The prognostic associations in the neoadjuvant setting of other anti-HER2 agents and combinations are unknown.
To determine associations between presence of TILs, pathological complete response (pCR), and event-free survival (EFS) end points in patients with early breast cancer treated with trastuzumab, lapatinib, or the combination.
The NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) randomly assigned 455 women with HER2-positive early-stage breast cancer between January 5, 2008, and May 27, 2010, to 1 of 3 neoadjuvant treatment arms: trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The primary end point used in this study was pCR in the breast and lymph nodes, with a secondary end point of EFS. We evaluated levels of percentage of TILs using hematoxylin-eosin–stained core biopsy sections taken at diagnosis (prior to treatment) in a prospectively defined retrospective analysis.
Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including
Of the 455 patients, 387 (85.1%) tumor samples were used for the present analysis. The median (interquartile range [IQR]) level of TILs was 12.5% (5.0%-30.0%), with levels lower in hormone receptor–positive (10.0% [5.0%-22.5%]) vs hormone receptor–negative (12.5% [3.0%-35.0%]) samples (
The presence of TILs at diagnosis is an independent, positive, prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both pCR and EFS end points.
Url:
DOI: 10.1001/jamaoncol.2015.0830
PubMed: 26181252
PubMed Central: 5551492
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 001E95
- to stream Pmc, to step Curation: 001D51
- to stream Pmc, to step Checkpoint: 000C58
- to stream PubMed, to step Corpus: 002B36
- to stream PubMed, to step Curation: 002A64
- to stream PubMed, to step Checkpoint: 002A64
- to stream Ncbi, to step Merge: 002844
- to stream Ncbi, to step Curation: 002844
- to stream Ncbi, to step Checkpoint: 002844
- to stream Main, to step Merge: 002678
- to stream Main, to step Curation: 002678
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab</title><author><name sortKey="Salgado, Roberto" sort="Salgado, Roberto" uniqKey="Salgado R" first="Roberto" last="Salgado">Roberto Salgado</name></author><author><name sortKey="Denkert, Carsten" sort="Denkert, Carsten" uniqKey="Denkert C" first="Carsten" last="Denkert">Carsten Denkert</name></author><author><name sortKey="Campbell, Christine" sort="Campbell, Christine" uniqKey="Campbell C" first="Christine" last="Campbell">Christine Campbell</name></author><author><name sortKey="Savas, Peter" sort="Savas, Peter" uniqKey="Savas P" first="Peter" last="Savas">Peter Savas</name></author><author><name sortKey="Nuciforo, Paolo" sort="Nuciforo, Paolo" uniqKey="Nuciforo P" first="Paolo" last="Nuciforo">Paolo Nuciforo</name></author><author><name sortKey="Aura, Claudia" sort="Aura, Claudia" uniqKey="Aura C" first="Claudia" last="Aura">Claudia Aura</name></author><author><name sortKey="De Azambuja, Evandro" sort="De Azambuja, Evandro" uniqKey="De Azambuja E" first="Evandro" last="De Azambuja">Evandro De Azambuja</name></author><author><name sortKey="Eidtmann, Holger" sort="Eidtmann, Holger" uniqKey="Eidtmann H" first="Holger" last="Eidtmann">Holger Eidtmann</name></author><author><name sortKey="Ellis, Catherine E" sort="Ellis, Catherine E" uniqKey="Ellis C" first="Catherine E." last="Ellis">Catherine E. Ellis</name></author><author><name sortKey="Baselga, Jose" sort="Baselga, Jose" uniqKey="Baselga J" first="Jose" last="Baselga">Jose Baselga</name></author><author><name sortKey="Piccart Gebhart, Martine J" sort="Piccart Gebhart, Martine J" uniqKey="Piccart Gebhart M" first="Martine J." last="Piccart-Gebhart">Martine J. Piccart-Gebhart</name></author><author><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name></author><author><name sortKey="Bradbury, Ian" sort="Bradbury, Ian" uniqKey="Bradbury I" first="Ian" last="Bradbury">Ian Bradbury</name></author><author><name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name></author><author><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26181252</idno><idno type="pmc">5551492</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551492</idno><idno type="RBID">PMC:5551492</idno><idno type="doi">10.1001/jamaoncol.2015.0830</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001E95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E95</idno><idno type="wicri:Area/Pmc/Curation">001D51</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001D51</idno><idno type="wicri:Area/Pmc/Checkpoint">000C58</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C58</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">002B36</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002B36</idno><idno type="wicri:Area/PubMed/Curation">002A64</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002A64</idno><idno type="wicri:Area/PubMed/Checkpoint">002A64</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002A64</idno><idno type="wicri:Area/Ncbi/Merge">002844</idno><idno type="wicri:Area/Ncbi/Curation">002844</idno><idno type="wicri:Area/Ncbi/Checkpoint">002844</idno><idno type="wicri:doubleKey">2374-2437:2015:Salgado R:tumor:infiltrating:lymphocytes</idno><idno type="wicri:Area/Main/Merge">002678</idno><idno type="wicri:Area/Main/Curation">002678</idno><idno type="wicri:Area/Main/Exploration">002678</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab</title><author><name sortKey="Salgado, Roberto" sort="Salgado, Roberto" uniqKey="Salgado R" first="Roberto" last="Salgado">Roberto Salgado</name></author><author><name sortKey="Denkert, Carsten" sort="Denkert, Carsten" uniqKey="Denkert C" first="Carsten" last="Denkert">Carsten Denkert</name></author><author><name sortKey="Campbell, Christine" sort="Campbell, Christine" uniqKey="Campbell C" first="Christine" last="Campbell">Christine Campbell</name></author><author><name sortKey="Savas, Peter" sort="Savas, Peter" uniqKey="Savas P" first="Peter" last="Savas">Peter Savas</name></author><author><name sortKey="Nuciforo, Paolo" sort="Nuciforo, Paolo" uniqKey="Nuciforo P" first="Paolo" last="Nuciforo">Paolo Nuciforo</name></author><author><name sortKey="Aura, Claudia" sort="Aura, Claudia" uniqKey="Aura C" first="Claudia" last="Aura">Claudia Aura</name></author><author><name sortKey="De Azambuja, Evandro" sort="De Azambuja, Evandro" uniqKey="De Azambuja E" first="Evandro" last="De Azambuja">Evandro De Azambuja</name></author><author><name sortKey="Eidtmann, Holger" sort="Eidtmann, Holger" uniqKey="Eidtmann H" first="Holger" last="Eidtmann">Holger Eidtmann</name></author><author><name sortKey="Ellis, Catherine E" sort="Ellis, Catherine E" uniqKey="Ellis C" first="Catherine E." last="Ellis">Catherine E. Ellis</name></author><author><name sortKey="Baselga, Jose" sort="Baselga, Jose" uniqKey="Baselga J" first="Jose" last="Baselga">Jose Baselga</name></author><author><name sortKey="Piccart Gebhart, Martine J" sort="Piccart Gebhart, Martine J" uniqKey="Piccart Gebhart M" first="Martine J." last="Piccart-Gebhart">Martine J. Piccart-Gebhart</name></author><author><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name></author><author><name sortKey="Bradbury, Ian" sort="Bradbury, Ian" uniqKey="Bradbury I" first="Ian" last="Bradbury">Ian Bradbury</name></author><author><name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name></author><author><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name></author></analytic><series><title level="j">JAMA oncology</title><idno type="ISSN">2374-2437</idno><idno type="eISSN">2374-2445</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><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>Antineoplastic Combined Chemotherapy Protocols (adverse effects)</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>Biomarkers, Tumor (antagonists & inhibitors)</term><term>Biomarkers, Tumor (metabolism)</term><term>Breast Neoplasms (drug therapy)</term><term>Breast Neoplasms (enzymology)</term><term>Breast Neoplasms (immunology)</term><term>Breast Neoplasms (mortality)</term><term>Breast Neoplasms (pathology)</term><term>Disease-Free Survival</term><term>Female</term><term>Humans</term><term>Lymphocytes, Tumor-Infiltrating (drug effects)</term><term>Lymphocytes, Tumor-Infiltrating (immunology)</term><term>Middle Aged</term><term>Neoadjuvant Therapy</term><term>Neoplasm Staging</term><term>Odds Ratio</term><term>Proportional Hazards Models</term><term>Prospective Studies</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 (metabolism)</term><term>Remission Induction</term><term>Retrospective Studies</term><term>Risk Factors</term><term>Time Factors</term><term>Trastuzumab (adverse effects)</term><term>Trastuzumab (therapeutic use)</term><term>Treatment Outcome</term><term>Young Adult</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>Facteurs de risque</term><term>Facteurs temps</term><term>Femelle</term><term>Humains</term><term>Induction de rémission</term><term>Inhibiteurs de protéines kinases (effets indésirables)</term><term>Inhibiteurs de protéines kinases (usage thérapeutique)</term><term>Jeune adulte</term><term>Lymphocytes TIL ()</term><term>Lymphocytes TIL (immunologie)</term><term>Marqueurs biologiques tumoraux (antagonistes et inhibiteurs)</term><term>Marqueurs biologiques tumoraux (métabolisme)</term><term>Modèles de hasards proportionnels</term><term>Odds ratio</term><term>Protocoles de polychimiothérapie antinéoplasique (effets indésirables)</term><term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term><term>Quinazolines (effets indésirables)</term><term>Quinazolines (usage thérapeutique)</term><term>Récepteur ErbB-2 (antagonistes et inhibiteurs)</term><term>Récepteur ErbB-2 (métabolisme)</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>Traitement néoadjuvant</term><term>Trastuzumab (effets indésirables)</term><term>Trastuzumab (usage thérapeutique)</term><term>Tumeurs du sein (anatomopathologie)</term><term>Tumeurs du sein (enzymologie)</term><term>Tumeurs du sein (immunologie)</term><term>Tumeurs du sein (mortalité)</term><term>Tumeurs du sein (traitement médicamenteux)</term><term>Études prospectives</term><term>Études rétrospectives</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><term>Trastuzumab</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Biomarkers, Tumor</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Biomarkers, Tumor</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Protein Kinase Inhibitors</term><term>Quinazolines</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Marqueurs biologiques tumoraux</term><term>Récepteur ErbB-2</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Lymphocytes, Tumor-Infiltrating</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Antinéoplasiques</term><term>Inhibiteurs de protéines kinases</term><term>Protocoles de polychimiothérapie antinéoplasique</term><term>Quinazolines</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes TIL</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Breast Neoplasms</term><term>Lymphocytes, Tumor-Infiltrating</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Marqueurs biologiques tumoraux</term><term>Récepteur ErbB-2</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><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>Protocoles de polychimiothérapie antinéoplasique</term><term>Quinazolines</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Disease-Free Survival</term><term>Female</term><term>Humans</term><term>Middle Aged</term><term>Neoadjuvant Therapy</term><term>Neoplasm Staging</term><term>Odds Ratio</term><term>Proportional Hazards Models</term><term>Prospective Studies</term><term>Remission Induction</term><term>Retrospective Studies</term><term>Risk Factors</term><term>Time Factors</term><term>Treatment Outcome</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Facteurs de risque</term><term>Facteurs temps</term><term>Femelle</term><term>Humains</term><term>Induction de rémission</term><term>Jeune adulte</term><term>Lymphocytes TIL</term><term>Modèles de hasards proportionnels</term><term>Odds ratio</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>Traitement néoadjuvant</term><term>Études prospectives</term><term>Études rétrospectives</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Importance</title><p id="P1">The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with adjuvant trastuzumab and chemotherapy. The prognostic associations in the neoadjuvant setting of other anti-HER2 agents and combinations are unknown.</p></sec><sec id="S2"><title>Objective</title><p id="P2">To determine associations between presence of TILs, pathological complete response (pCR), and event-free survival (EFS) end points in patients with early breast cancer treated with trastuzumab, lapatinib, or the combination.</p></sec><sec id="S3"><title>Design, Setting, and Participants</title><p id="P3">The NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) randomly assigned 455 women with HER2-positive early-stage breast cancer between January 5, 2008, and May 27, 2010, to 1 of 3 neoadjuvant treatment arms: trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The primary end point used in this study was pCR in the breast and lymph nodes, with a secondary end point of EFS. We evaluated levels of percentage of TILs using hematoxylin-eosin–stained core biopsy sections taken at diagnosis (prior to treatment) in a prospectively defined retrospective analysis.</p></sec><sec id="S4"><title>Main Outcomes and Measures</title><p id="P4">Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including <italic>PIK3CA</italic> genotype.</p></sec><sec id="S5"><title>Results</title><p id="P5">Of the 455 patients, 387 (85.1%) tumor samples were used for the present analysis. The median (interquartile range [IQR]) level of TILs was 12.5% (5.0%-30.0%), with levels lower in hormone receptor–positive (10.0% [5.0%-22.5%]) vs hormone receptor–negative (12.5% [3.0%-35.0%]) samples (<italic>P</italic> = .02). For the pCR end point, levels of TILs greater than 5% were associated with higher pCR rates independent of treatment group (adjusted odds ratio, 2.60 [95% CI, 1.26-5.39]; <italic>P</italic> = .01). With a median (IQR) follow-up time of 3.77 (3.50-4.22) years, every 1% increase in TILs was associated with a 3% decrease in the rate of an event (adjusted hazard ratio, 0.97 [95% CI, 0.95-0.99]; <italic>P</italic> = .002) across all treatment groups.</p></sec><sec id="S6"><title>Conclusions and Relevance</title><p id="P6">The presence of TILs at diagnosis is an independent, positive, prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both pCR and EFS end points.</p></sec><sec id="S7"><title>Trial Registration</title><p id="P7"><ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</ext-link> Identifier: NCT00553358</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Aura, Claudia" sort="Aura, Claudia" uniqKey="Aura C" first="Claudia" last="Aura">Claudia Aura</name><name sortKey="Baselga, Jose" sort="Baselga, Jose" uniqKey="Baselga J" first="Jose" last="Baselga">Jose Baselga</name><name sortKey="Bradbury, Ian" sort="Bradbury, Ian" uniqKey="Bradbury I" first="Ian" last="Bradbury">Ian Bradbury</name><name sortKey="Campbell, Christine" sort="Campbell, Christine" uniqKey="Campbell C" first="Christine" last="Campbell">Christine Campbell</name><name sortKey="De Azambuja, Evandro" sort="De Azambuja, Evandro" uniqKey="De Azambuja E" first="Evandro" last="De Azambuja">Evandro De Azambuja</name><name sortKey="Denkert, Carsten" sort="Denkert, Carsten" uniqKey="Denkert C" first="Carsten" last="Denkert">Carsten Denkert</name><name sortKey="Eidtmann, Holger" sort="Eidtmann, Holger" uniqKey="Eidtmann H" first="Holger" last="Eidtmann">Holger Eidtmann</name><name sortKey="Ellis, Catherine E" sort="Ellis, Catherine E" uniqKey="Ellis C" first="Catherine E." last="Ellis">Catherine E. Ellis</name><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name><name sortKey="Nuciforo, Paolo" sort="Nuciforo, Paolo" uniqKey="Nuciforo P" first="Paolo" last="Nuciforo">Paolo Nuciforo</name><name sortKey="Piccart Gebhart, Martine J" sort="Piccart Gebhart, Martine J" uniqKey="Piccart Gebhart M" first="Martine J." last="Piccart-Gebhart">Martine J. Piccart-Gebhart</name><name sortKey="Salgado, Roberto" sort="Salgado, Roberto" uniqKey="Salgado R" first="Roberto" last="Salgado">Roberto Salgado</name><name sortKey="Savas, Peter" sort="Savas, Peter" uniqKey="Savas P" first="Peter" last="Savas">Peter Savas</name><name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002678 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002678 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:5551492
|texte= Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26181252" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |