Abstract P2-08-29: Defining a signature of residual risk following endocrine treatment in the tamoxifen and exemestane adjuvant multinational (TEAM) trial
Notice bibliographique
Résumé
Abstract Introduction: There are a number of commercially-available tests to stratify risk for women diagnosed with early breast cancer. While such "Generation I" tests are increasingly being used, a consensus is growing that these tests are moderately accurate in assessing risk. Moreover, Generation I tests fail to direct more personalized treatment. Therefore, there is a clear need for more informative "Generation II" tests that better assess risk, also on the long term, and provide theranostic targets. To this end, we have performed an mRNA abundance-based analysis trained in the 790 patients of the UK TEAM cohort to identify a signature of residual risk , to be validated in the remaining 3000 patients from the TEAM pathology study. Methods: RNA extracted from the tumors of respective TEAM pathology study patients were profiled using a 165-gene NanoString code set. The gene list was compiled from targets that comprise many of the existing risk assessment tests, in addition to genes known to be of importance for breast cancer pathogenesis. Signal intensities were normalized using the R statistical environment; 336 different combinations of preprocessing methods were assessed and the most optimal method selected using unbiased criteria. A10-fold cross-validation approach, in combination with a network-based patient risk score calculation formula, was used to derive a 95-gene signature. Briefly, genes were first filtered based on a Cox regression p-value threshold of 0.25; the sum of the weighted mRNA abundance levels of the result genes was calculated for each patient as the risk score. Patient-wise risk scores were then used in a multivariate Cox proportional hazards model along with clinical covariates such as age, grade, HER2 status and nodal status, using DRFS truncated to 10 years as an end-point. Results: Univariate survival analysis revealed a number of significantly prognostic candidates. The resulting 95-gene signature identified in the training set, stratified patients into high and low risk with an HRhigh of 2.74 (p<2.06 x10-4) when adjusted for age, grade, HER2 status and nodal status; resulting in an AUC of 0.73. Modular analyses of the genes comprising the 95-gene signature identified pathways associated with receptor tyrosine kinase signalling, regulation of cell cycle, and the spindle assembly checkpoint. Additionally, the composition of the gene-list made it possible to characterize the patients into their intrinsic subtypes and to determine their relative risk for recurrence relative to assessment tools available today . The validation of the 95-gene signature will be conducted in the remaining samples in the TEAM pathology study using the bioinformatics strategy described above. Conclusions: The impact of test-guided therapy using multi-parametric tests is increasingly being felt in the clinic, and is reshaping modern health-care economics. A successful Generation II multi-parametric test will better discriminate those that are truly at high risk for recurrence following endocrine therapy and indicate potential therapeutic options for intervention for those who would not benefit from current modalities. Citation Format: Bayani J, Yao CQ, Quintayo MA, Haider S, Brookes CL, Yan F, van de Velde CJH, Hasenburg A, Kieback DG, Markopoulos C, Dirix L, Seynaeve C, Boutros PC, Rea DW, Bartlett JMS. Defining a signature of residual risk following endocrine treatment in the tamoxifen and exemestane adjuvant multinational (TEAM) trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-29.
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 | 0,003 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
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 ».