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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,001 |
| 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 tête enseignante, 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 ».