Abstract P3-10-11: Clinical implications of 63-gene signature associated with response to PARP inhibition in triple-negative and luminal B breast cancer
Notice bibliographique
Résumé
Abstract Background: Two recent randomized phase 3 trials have demonstrated that treatment with PARP inhibitors results in an improvement in progression-free survival (PFS) in metastatic, BRCA-mutant, HER2-negative breast cancer patients. We have previously identified a pathway-enriched 63-gene expression signature predictive of response to olaparib in seven patient-derived xenograft breast tumors, with a high overall accuracy of 86%. We found that the prevalence of our gene signature was 45% in a cohort of triple-negative breast cancer (TNBC) patients. We wanted to better understand if there were correlations between our 63-gene signature and other known prognostic markers and to determine the prognostic significance of our mutational gene signature in different PAM50 breast cancer subtypes. Methods: We used a publicly available dataset from the NCI GDC Data Portal of TNBC patients (n = 82) to undertake clinico-pathological correlations with our 63-gene expression signature. We correlated the presence or absence of the signature with age, tumor size, lymph node status, and stage using chi2 analysis, in addition to overall survival (OS) and PFS with STATA SE. We also correlated our gene signature with known TNBC subtypes from TNBCtype. Using the METABRIC cohort (n = 2509), we looked at the mutational frequency of our gene set in cBioPortal in different breast cancer subtypes and determined the prognostic value in each subtype. Results: We did not find any statistically significant correlations between the 63-gene expression signature and age, tumor size, lymph node status, or stage amongst the 82 TNBC patients. All TNBC subtypes including 2 basal-like, immunomodulatory, low androgen receptor, 2 mesenchymal-based, and unspecified were identified in both gene-signature predicted sensitive and resistant groups, but there were no statistically significant differences between groups. The median follow-up of the TNBC cohort was 24 months, and no statistically significant associations were identified with OS or PFS. In the METABRIC cohort, the mutational frequency of any of the 63 genes for the following subgroups was identified: basal (n = 209), 85.2%; HER2+ (n = 224), 68.8%; claudin-low (n = 218), 48.2%; luminal B (n=475), 25.1%; and luminal A (n=700), 12.7%. The median follow-up of the METABRIC cohort was 127 months. We found that patients with a mutation in any of the 63 genes demonstrated a poorer overall survival, 122.8 months, in comparison to patients without any mutation, 164.6 months (P = 0.0002). In particular, luminal B patients with a mutation in any of these genes demonstrated a poorer overall survival, 90.0 months, in comparison to patients without a mutation, 132.1 months (P = 0.009). No statistically significant difference in overall survival was observed for patients with or without any mutation amongst the luminal A subtype (P = 0.26). Conclusion: We found that patients with a mutation from our 63-gene set demonstrated a worse prognosis in comparison to patients without a mutation amongst the luminal B subtype. This is suggestive that there may be a role for our 63-gene signature to select patients amongst the luminal B subtype who may benefit from PARP inhibition. Citation Format: Beniey M, Marois F, Haque T, Hassan S. Clinical implications of 63-gene signature associated with response to PARP inhibition in triple-negative and luminal B breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-11.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».