Abstract C184: Thyroid hormone receptors: Future targets for breast cancer therapy?.
Notice bibliographique
Résumé
Abstract Introduction: Thyroid receptors (TR) have been documented in breast cancer tissue. Given their role in cell metabolism and proliferation, they may serve as future therapeutic targets. Prior to targeting TRs for therapy, their prevalence and degree of expression must be elucidated. In this study, the expression and sub-cellular location of three TR isoforms (TRA1, TRA2, TRB1) in breast cancer tissue is documented and correlated to standard pathological and clinical prognostic markers. Methods: 131 archived breast tumors were selected sequentially starting from January 2007, to allow for collection of 5-year overall survival (OS) and disease-free survival (DFS) data. The tumors were assessed retrospectively for TRA1, TRA2 and TRB1 expression by immunohistochemistry, using commercially available antibodies. Nuclear versus cytoplasmic location was noted. The Allred score of each tumor was assessed in triplicate; an average score ≥5 was considered significant in the statistical analysis. TR expression was correlated with pathological markers (ER/PR and Her2/neu positivity, tumor size, grade, nodal involvement, lymphovascular invasion, mitotic count) and clinical factors (age, OS, DFS) using correlation analyses and binary regression models. Results: The age of patients was 65±15 (mean± standard deviation) years. The majority had T1c (31%) or T2 (56%) disease, and 39% had lymph node involvement. 60% of tumors were ER positive and 13% were Her2/neu positive. TRs were expressed to some extent in 130 of 131 assessed breast tumors; TRA1 was highly expressed (Allred score ≥5) in 81% of tumors, while TRA2 and TRB1 were highly expressed in 51% and 29% of tumors, respectively. TRA1 and TRA2 were expressed in the nucleus, while 95% of TRB1 receptors were expressed in the cytoplasm. Cytoplasmic TRB1 expression was associated with a mitotic count <10 [OR 0.4 (95%CI 0.20-0.93), p=0.03], but not with other variables. High TRA2 expression was associated with ER [OR 5.5 (95%CI 2.2-13.7), p<0.01] and PR [OR 5.3 (95%CI 2.4-11.8), p<0.01] positivity, and also 5-year DFS [OR 2.6 (95%CI 1.1-6.1), p=0.03]. Conversely, low TRA expression was associated with Her2/neu positivity [OR 3.2, (95%CI 1.0-9.5), p=0.04], high tumor grade [OR 6.0, (95%CI 2.3-15.2), p<0.01] and a mitotic count >10 [OR 2.8, (95%CI 1.4-5.8), p=0.05]. There was no significant association between TR expression and tumor size, lymph node involvement or OS. Conclusion: Thyroid receptors are widely expressed in breast cancer and they are known to influence cellular proliferation. High TRA2 expression is statistically significant in predicting favorable pathologic markers and even 5-year DFS. As with ER, its favorable prognostic profile should not exclude TRA2 as a therapeutic target; it may have the potential to expand our armamentarium of hormone directed therapies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C184. Citation Format: Katarzyna J. Jerzak, Anita Bane, Bindi Dhesy-Thind. Thyroid hormone receptors: Future targets for breast cancer therapy?. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C184.
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 | 0,001 | 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 | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,019 | 0,005 |
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 ».