Abstract P2-11-03: Predictive significance of an optimized immunohistochemical panel for basal-like breast cancer on the CCTG MA.12 phase III randomized clinical trial
Notice bibliographique
Résumé
Abstract Background: Tamoxifen and aromatase inhibitors constitute the backbone of treatment for estrogen receptor positive early stage breast cancers based on immunohistochemical (IHC) results. While these therapies significantly reduce the risk of relapse of breast cancer, they have toxicities and add to costs. Gene expression profiling assays are widely used to quantify risk and support targeted therapies for luminal breast cancers treated with adjuvant endocrine therapy. In a prospective-retrospective analysis of the phase III CCTG MA.12 clinical trial (randomizing premenopausal women treated with adjuvant chemotherapy, to either tamoxifen or placebo for 5 years), luminal subtype by PAM50 was significantly predictive for tamoxifen benefit. However, IHC classification (as estrogen receptor positive) could not demonstrate a statistically significant benefit from tamoxifen over placebo. More accurate IHC biomarkers incorporating nestin positivity or loss of inositol polyphosphate-4-phosphate (INPP4B) have recently been optimized to identify the basal-like intrinsic subtype of breast cancer regardless of ER/PR/HER2 status. In this study, we examined the capacity of these basal biomarkers to identify intrinsic subtype and predict benefit from adjuvant tamoxifen vs. placebo in the CCTG MA.12 clinical trial Methods:492 formalin-fixed paraffin embedded blocks of primary tumor from patients randomized in the CCTG MA.12 trial were used to build tissue microarrays. IHC staining for nestin and INPP4B was done according to published methods, and interpretation was performed by pathologists with no access to molecular data. The performance of the nestin and INPP4B panel was assessed against PAM50 gene expression assay as a standard reference. A prespecified statistical plan was executed independently by the Canadian Cancer Trials Group, testing the primary hypothesis that patients with basal breast cancer, when defined as “positive for nestin or negative for INPP4B,” would not benefit from tamoxifen (primary endpoint: disease-free survival).Results: 366 primary tumor samples from the CCTG MA.12 had a full dataset available for IHCbiomarker evaluation, PAM50 subtype and clinical outcomes. Positive staining of nestin or loss of INPP4B was observed in 47 (13%) of the total cases and was significantly associated with poor prognostic factors including high grade, younger age, ER negativity, triple negative and core basal IHC status (p<0.01). “Nestin+ or INPP4B-” status was significantly associated with basal-like PAM50 gene expression subtype, while the other cases (nestin- and INPP4B+) were significantly associated with PAM50 luminal subtype. Patients assigned as basals by “nestin+ or INPP4B-” IHC status did not demonstrate a benefit from adjuvant tamoxifen vs. placebo (HR=1.39, 95%CI [0.37-5.26], p=0.63), whereas “nestin- and INPP4B+” cases displayed a significantly higher benefit from adjuvant tamoxifen vs. placebo (HR=0.67, 95% CI [0.45-0.98], p=0.04), (p-interaction=0.87). While, in this trial, ER clinical status as determined in community hospitals or centrally by single biomarker IHC was not significantly predictive for tamoxifen benefit, patients classified as IHC non-basal “nestin- and INPP4B+” within the ER+ subgroup did benefit from addition of tamoxifen (HR=0.62, 95%CI [0.38-1.01], p=0.05).Conclusions:The nestin/INPP4B IHC panel offers a feasible and inexpensive methodology to accurately identify intrinsic subtype of breast cancer. Patients assigned as IHC basal by this panel did not display a superior survival when treated with tamoxifen vs. placebo in the adjuvant setting. Within the ER+ subgroup, these cases could potentially be spared the side effects of currently recommended endocrine therapies that do not benefit this group of patients. Citation Format: Karama Asleh, Dongxia Gao, Vivien H Bramwell, Dongsheng Tu, Lois E Shepherd, Torsten O Nielsen. Predictive significance of an optimized immunohistochemical panel for basal-like breast cancer on the CCTG MA.12 phase III randomized clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-03.
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 | 0,007 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,002 | 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 ».