Abstract P4-11-06: TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial
Notice bibliographique
Résumé
Abstract Background: TLE3, a nuclear transcriptional repressor downstream of the WNT signaling pathway, has been identified as a candidate predictive biomarker of taxane benefit in early breast cancer. However, robust clinical evidence is required before implementing novel diagnostic biomarkers. We tested the hypothesis that TLE3 predicts for benefit from taxane containing polychemotherapy in the NCIC CTG MA.21 clinical trial. Methods: MA.21 accrued 2104 patients [701 each to cyclophosphamide, epirubicin, and 5 fluorouracil (CEF) and epirubicin and cyclophosphamide with filgrastim and epoetin alfa followed by paclitaxel (EC/T), 702 to doxorubicin and cyclophosphamide followed by paclitaxel (AC/T)] who were followed median 8 years by the final analysis. EC/T and CEF were not significantly different (p= 0.69) while AC/T was inferior to both EC/T and CEF (respectively, p=0.001 and p=0004). Tissue microarrays were constructed from 1097 of the 2104 patients. Patient characteristics were well balanced between those included in the TLE3 analysis and the full trial population. Up to four 0.6 mm tumor cores were stained for TLE3 expression by immunohistochemistry using a previously validated methodology. Continuous visual TLE3 score was the average % positive stain across all cores, while continuous automated score was sum of cells with positive stain/ total cells assessed in all cores. The primary objective used the EC/T (taxane-containing) and CEF (non-taxane; similar dose-density) arms for a test of predictive effect of TLE3 on relapse free survival. TLE3 was positive if >30% of cells stained, the established cut-point, with data available from at least 1 core/tumor. We also examined quartile cut-points, multivariate effects of TLE3, and compared AC/T and CEF. Results: MA.21 patients had 83.2% TLE3+ tumors by visual score and 80.6% TLE3+ by automated image analysis greater than the predicted rate of TLE3 positivity (58.6%) based on prior series and adjusting for clinicopathological features. TLE3 expression was significantly positively associated with ER expression (91.2% of ER+ were TLE3+; p<0.0001). There was no evidence of a predictive effect of TLE3 expression with respect to taxane benefit using the established 30% cut-point, nor quartile cut-points. The treatment and TLE3 interaction term for the EC/T by CEF comparison was not significant (stratified p=0.68, for manual TLE3; p=0.44, for automated TLE3). Conclusions: MA.21 patients had a much higher proportion of TLE3+ tumors than anticipated. Multiple assessments of TLE3 cut-points yielded no evidence that it was predictive of taxane benefit. In our trial TLE3 expression was not a biomarker for taxane benefit (EC/T vs CEF) when using either previously established or common quartile cut-offs for expression in breast cancer. Citation Format: John MS Bartlett, Torsten O Nielsen, Dongxia Gao, Karen A Gelmon, Mary Anne Quintayo, Jane Starczynski, Lei Han, Margot J Burnell, Mark N Levine, Lois E Shepherd, Judy-Anne W Chapman. TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-06.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».