Abstract P2-10-02: Basal biomarkers nestin and INPP4b predict gemcitabine benefit in metastatic breast cancer: Results from the phase III SBG0102 clinical trial
Notice bibliographique
Résumé
Abstract Background: A growing body of evidence is suggesting that basal-like and triple negative breast cancers may be particularly sensitive to nucleoside analogues (gemcitabine, capecitabine). In a prospective-retrospective analysis of the phase III SBG0102 clinical trial randomizing metastatic breast cancer patients to gemcitabine plus docetaxel (GD) or to higher-dose single agent docetaxel (D), patients with basal-like breast cancer by PAM50 gene expression had significantly better overall survival (OS) in the gemcitabine arm. By immunohistochemistry (IHC), triple negative status was not predictive, but is a poor surrogate for the basal-like intrinsic subtype. More accurate IHC biomarkers have since become available defining basal-like breast cancers by nestin positivity or by loss of inositol polyphosphate-4-phosphate (INPP4b). Methods: Formalin-fixed paraffin embedded blocks of primary tumor tissue corresponding to 270 of the 337 patients participated in the SBG0102 trial were used to build tissue microarrays. IHC staining and interpretation for nestin and INPP4b by pathologists (who had no access to clinical data) followed published methods. A prespecified statistical plan was executed independently by Danish Breast Cancer Group statisticians, testing the primary hypothesis that patients with basal breast cancer – defined as positive for nestin or negative for INPP4b, regardless of ER/PR/HER2 status – would have superior OS on the GD treatment arm when compared to the D treatment arm by interaction test. Secondary outcomes included time to tumor progression (TTP) and response rate. Kaplan-Meier method with log-rank test of nestin and INPP4b status was used to measure OS and TTP. Forest plots were used to visualize predictive capacities relative to IHC markers and treatment effects. Results: Two hundred fifty two cases were evaluable for this study, among which 38 (15%) had been classified as basal-like, 45 (18%) as HER2-Enriched, 74 (29%) as luminal A and 91 (36%) as luminal B by PAM50. Among 241 cases being evaluable for both IHC nestin and INPP4b markers, positive staining of nestin or loss of INPP4b was observed in 43 (17%) of the total cases and was significantly associated with PAM50 basal-like subtype (p<0.0001). Within a median follow up of 13 years, patients assigned as IHC-basal by virtue of being “nestin+ or INPP4b-” demonstrated a significantly lower OS when compared to non-basal cases defined as “nestin- and INPP4b+” (HR=2.45, 95% CI: 1.47-4.07) (p=0.0006). The IHC-basal patients did much better on the GD vs. the D arm (HR=0.36, 95% CI: 0.19-0.68) whereas there was no such difference in outcomes for other patients (HR=0.99). The interaction test was significant (p-interaction<0.005). Conclusions: The nestin/INPP4b IHC panel offers a practical and inexpensive technology to identify basal-like patients. In the metastatic setting, women with IHC-basal breast cancers defined using these markers have superior overall survival when randomized to gemcitabine-containing chemotherapy compared to docetaxel alone. Citation Format: Asleh-Aburaya K, Lyck Carstensen S, Burugu S, Gao D, Tykjær Jørgensen CL, Won JR, Jensen M-B, Balslev E, Lænkholm A-V, Nielsen DL, Ejlertsen B, Nielsen TO. Basal biomarkers nestin and INPP4b predict gemcitabine benefit in metastatic breast cancer: Results from the phase III SBG0102 clinical trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-02.
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 | 0,003 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 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 ».