Abstract P1-07-13: Prognostic relevance of statistically standardized estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in tamoxifen(TAM)-treated NCIC CTG MA.14 patients
Notice bibliographique
Résumé
Abstract Background: Poor inter-laboratory comparability of common clinically used breast cancer biomarkers led to a proposal of statistical standardization (SS) of laboratory results, similar to bone mineral density (BMD) z-scores. This analysis is the first utilization of SS in a trial where all women received TAM. Methods: MA.14 allocated 667 postmenopausal women to TAM +/− Octreotide LAR (OCT) based on locally determined ER/PR, without HER2 status. At 9.8 yrs median follow-up, the secondary endpoint of relapse-free survival (RFS) had a non-significant hazard ratio (HR) for TAM-OCT to TAM of 0.87 (95% CI 0.63–1.21; p = 0.40). 299 patients who were representative of MA.14 patients by treatment and stratification factors (exact Fisher p-values=0.19–0.90) had their tumors centrally assessed for ER, PR, and HER2 by RT-PCR. Continuous values were used for SS of each biomarker. Univariate (uni) assessment used similar categorizations as those for BMD, assigning ER/PR/HER2 values by number of standard deviations (SD) about the mean (Group 1, z-score ≥1.0 SD below mean; Group 2, z-score <1.0 SD below mean; Group 3, z-score ≤1.0 SD above mean; Group 4, z-score >1.0 SD above mean). A log-rank statistic was used to test for differences between SS biomarker groups with K-M plots for graphical description. Multivariate (multi) effects of SS biomarkers and baseline patient characteristics on RFS were examined with exploratory (un)stratified Cox step-wise forward regression, adding a factor if likelihood ratio criterion was p ≤ 0.05. Sensitivity analyses used a prior external HER2+ cut-point of ≥1.32 SD. Results: 292 patient samples passing internal analytical quality control were included in this analysis. Uni analyses indicated SS ER was not associated with RFS (p = 0.31). SS PR had a significant uni effect on RFS [p = 0.03; Group 4 compared to Group 1, HR of 0.33 (95% CI 0.12–0.90); Group 3 compared to Group 1, HR of 0.42 (95% CI 0.21–0.83); and Group 2 compared to Group 1 HR of 0.70 (95%CI 0.36–1.37)]. SS HER2 also had a significant uni effect on RFS [p = 0.004; Group 4 compared to Group 1, HR of 0.90 (95% CI 0.37–2.16)]; Group 3 compared to Group 1, HR of 0.39 (95% CI 0.18–0.84); and, Group 2 compared to Group 1, HR of 0.34 (95% CI 0.16–0.70)]. Multi stratified/unstratified Cox models indicated T1 tumours (p = 0.02/p = 0.0002) and higher SS PR (p = 0.02/0.01) were associated with significantly longer RFS; other unstratified results showed that N-ve patients had better RFS (p < .0001), while local ER/PR status did not impact RFS (p > 0.05). The HER2+ cut-point of ≥1.32 SD indicated directionally worse RFS (uni p-value=0.05; multi p-value=0.06). Discussion: In MA.14, all women received TAM. Local ER/PR status using categorical or semi-quantitative values did not impact RFS. A statistically standardized approach using continuous centralized ER, PR, HER2 by RT-PCR demonstrated that increasing PR values were associated with better RFS. Evaluation in other trials may provide support for this methodology. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-13.
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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 | 0,004 |
| 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) | 0,003 | 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 ».