Abstract P6-19-01: Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
Notice bibliographique
Résumé
Abstract Introduction: Male breast cancer (MBC) is a rare disease accounting for less than 1% of all breast cancers (BC) and 1% of all cancers in males. The clinical management is largely extrapolated from female BC. Several multigene assays are increasingly used to guide clinical treatment decisions in female BC, however there is little data on the utility of these tests in MBC. Methods: Here we present the gene expression results of 380 M0, ER+ve, HER2-ve MBCs enrolled in the Part 1 (retrospective joint analysis) International Male Breast Cancer Program of 1483 patients diagnosed between 1990-2010 (Cardoso et al. Annals of Oncology, 2018). Using a custom Nanostring™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDx® and Mammaprint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by Bayani and Yao et al (npjBreast Cancer, 2017). Survival outcomes by risk classification were analyzed using Cox models with time-dependent covariates when the proportional hazard assumption was not met and adjusted for clinical and treatment variables. Results: Prosigna-like risk scores identified 99 (26.1%) as low-risk, 159 (41.8%) as intermediate-risk, and 122 (32.1%) as high-risk. Using the TAILORx cut-off (25) for OncotypeDx-like risk of recurrence scoring, 158 (41.6%) were identified as low-risk, while 222 (58.4%) were identified as high-risk. MammaPrint-like results identified 175 (46.1%) as low-risk and 205 (53.9%) as high-risk. Overall, patients classified as high-risk had higher grade, more nodal involvement, larger tumors, and more frequently treated with chemotherapy than low-risk patients. Survival analyses demonstrated clear clinical utility for each test, showing patients at high-risk with poor relapse-free survival (RFS) as compared to patients classified as low-risk: Prosigna-like RFS at 3-years (HR=2.20, 95% CI, 1.28-3.80); Oncotype-like RFS at 3-years (HR=1.92, 95% CI, 1.17-3.17); MammaPrint-like RFS (HR=1.51, 95% CI, 1.00-2.27); with similar findings for distant relapse-free survival (DRFS) and overall survival (OS). Across outcomes and all gene signatures, patients with concordant Low/Low risk classification had better prognosis than those with concordant High/High risk classification. PAM50 intrinsic subtyping identified 147 (38.7%) as Luminal A, 57 (15.0%) as Luminal B, 80 (21.1%) as Her2-enriched and 96 (25.3%) as Basal-like; showing overall 34.5% concordance to clinic-pathological subtyping by central pathology (95% CI, 29.7%-39.5%). Comparison between the tests in the MBC cohort and a comparable cohort of female BC from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial processed in the same way will be presented. Conclusion: Common transcriptomic assays designed to assess residual risk, validated in female BC, provide similar information in male BC patients. Not surprisingly, disagreement between test results at the individual patient level was observed. To our knowledge, this is the largest study of MBC assayed to generate risk scores of the current commercial BC tests to demonstrate their clinical utility and their differences and similarity to female BC. This work has been funded by the Breast Cancer Research Foundation (BCRF). Citation Format: Bayani J, Poncet C, Yao CQ, Crozier C, Anouk N, Piper T, Cunningham C, Sobol M, Aebi S, Benstead K, Bogler O, Dal Lago L, Fraser J, Hilbers FH, Hedenfalk I, Korde L, Linderholm B, Martens J, Middleton L, Murray M, Kelly C, Nilsson C, Nowaczyk M, Peeters S, Peric A, Porter P, Schröder C, Rubio IT, Ruddy KJ, van Asperen C, Van Den Weyngaert D, van Deurzen C, van Leeuwen-Stok E, Vermeij J, Winer E, Boutros PC, Giordano SH, Cardoso F, Bartlett JM. Evaluation of multiple transcriptomic gene risk signatures in male 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 P6-19-01.
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 | 0,001 | 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 | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».