Abstract S1-08: High risk premenopausal luminal A breast cancer patients derive no benefit from adjuvant chemotherapy: Results from DBCG77B randomized trial
Notice bibliographique
Résumé
Abstract Aim: To determine the predictive value of intrinsic subtypes for response to adjuvant chemotherapy using specimens from a randomized clinical trial. Background: Several studies have shown distinct clinical profiles of intrinsic breast cancer subtypes. The Luminal A subtype has a favorable prognosis with higher survival rate and lower recurrence in comparison to other breast cancer subtypes (luminal B, HER2 and basal-like). In addition, there is mounting evidence suggesting that intrinsic breast cancer subtypes differ in their responsiveness to adjuvant chemotherapy. Based on these data, we hypothesized that Luminal A breast cancer patients derive no benefit from adjuvant chemotherapy whereas other intrinsic subtypes do. Randomized breast cancer trials with a no chemotherapy arm and available tissues are rare, but represent the best materials to test for markers predicting chemotherapy benefit. The 77B clinical trial from the Danish Breast Cancer Cooperative Group (DBCG) offers a unique opportunity to test such hypotheses as it randomized 1146 premenopausal women, who had positive axillary lymph nodes or tumors >5 cm, to two chemotherapy arms (single-agent oral cyclophosphamide, or cyclophosphamide-methotrexate-fluorouracil (CMF)), and two no chemotherapy arms (levamisole, or no agent). All arms included radiotherapy but no endocrine therapy. Methods: We performed a full intrinsic subtype analysis on the 709 breast cancers available from DBCG77B on tissue microarrays using previously published, locked-down immunohistochemical (IHC) methods and intrinsic subtype definitions based on ER, PR, HER2, Ki67 and basal markers (Prat et al. JCO 2014). Biomarker scoring was performed in Vancouver by researchers with no access to the clinical database. A full statistical plan was prespecified in the Material Transfer Agreement and executed accordingly by the DBCG Statistical Office. 10-year invasive disease-free survival (IDFS) was the primary end point in DBCG77B; overall survival was also a predefined endpoint. The primary hypothesis was to assess interaction between benefit of chemotherapy (chemotherapy yes vs no) and subtype (Luminal A vs non-luminal A). This was analyzed in multivariate Cox proportional hazards models using the Wald test for interaction. Results: 709 patients had tissue available and completed IHC intrinsic subtyping. The effect of chemotherapy in this subset of patients was similar to the original trial: hazard ratio 0.56, favoring chemotherapy for 10-yr IDFS. IHC classified 165 as luminal A, 319 luminal B, 58 HER2E and 91 as triple negative (including 82 core basal). Patients with luminal A breast tumors did not benefit from chemotherapy (HR = 1.07, 95% CI = 0.53-2.14, p = 0.86), whereas patients with non-luminal A subtypes did (HR = 0.50, 95% CI = 0.38-0.66, p < 0.001). This heterogeneity was statistically significant (p=0.048). A similar trend for 25-yr OS was seen, although not significant. Conclusions: In a formal prospective-retrospective analysis of the DBCG 77B study randomizing women to adjuvant cyclophosphamide-based chemotherapy vs. no chemotherapy arms, patients with non-luminal A breast tumors (defined by IHC), but not luminal A tumors, benefit from adjuvant chemotherapy. Citation Format: Nielsen TO, Jensen [lrm] M-B, Gao D, Leung S, Burugu S, Liu S, Tykjær Jørgensen CL, Balslev E, Ejlertsen B. High risk premenopausal luminal A breast cancer patients derive no benefit from adjuvant chemotherapy: Results from DBCG77B randomized trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S1-08.
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 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,003 |
| 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 | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,002 |
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 ».