Abstract P2-11-02: Breast Cancer Index predicts benefit from extended endocrine therapy in HR+ breast cancer
Notice bibliographique
Résumé
Abstract Background: Optimizing the duration of adjuvant endocrine therapy in patients diagnosed with early stage hormone receptor-positive (HR+) breast cancer requires improved approaches to individualize disease profile and to reduce any unnecessary treatment burden for patients. Current clinical practice guidelines recommend 10 years of adjuvant endocrine therapy for most patients unless there are characteristics of low risk disease. However, approximately 2/3rds of patients have favorable long-term outcomes after completing 5 years of adjuvant therapy. Therefore, consideration of the risk-benefit profile for each patient is critical to identify who may be spared extended endocrine therapy (EET) and its associated toxicities, and which patients will benefit from an additional 5 years of endocrine therapy. The Breast Cancer Index (BCI) is a gene expression-based signature that stratifies patients based on the risk of overall (0-10y) and late (post-5y) distant recurrence (DR) and predicted the likelihood of benefit from extended endocrine therapy in MA.17. The translational-aTTom (Trans-aTTom) study is a multi-institutional, prospective-retrospective study to validate the predictive ability of BCI by HOXB13/IL17BR (H/I) status for EET benefit in early stage HR+, N0 and N+ breast cancer. Methods: Patients treated in the aTTom (Adjuvant Tamoxifen - To Offer More?) trial with available primary tumor tissue were eligible. Biospecimens were retrospectively collected from aTTom study sites and centrally assessed for ER, PR and HER2 status. Median follow-up was 12.6 years. Primary and secondary endpoints were recurrence-free interval (RFI) and disease-free interval (DFI), respectively. Statistical significance level was set at 0.0336 as per statistical analysis plan. Weighted Kaplan-Meier and Cox proportional hazards regression analysis with time-varying coefficients were used to test the predictive activity of BCI by HOXB13/IL17BR (H/I) status (High vs Low). Likelihood ratio test based on Cox regression was used to evaluate treatment by biomarker interaction. Results: Archived tumor specimens from 3328 patients were collected across 62 aTTom trial sites, representing 48% of the parent trial population. Central testing and assessment of ER, PR, HER2, and BCI resulted in 2445 HR+ patients (1367 N0, 789 N+, 289 nodal status unknown) in the overall cohort. At final analysis, the study remained underpowered for evaluating BCI predictive performance in the overall cohort due to an observed limited effect size that was smaller than planned and did not recapitulate the parent aTTom trial. However, evaluation of BCI predictive performance in the updated N+ subset (N=789) showed that patients classified as BCI(H/I)-High (N=404, 51%) experienced a statistically significant benefit from 10y vs 5y of tamoxifen (9.7% RFI: HR=0.33 [95% CI 0.14-0.75]; P=0.016), whereas those classified as BCI(H/I)-Low showed no significant benefit (-1.2% RFI; HR=1.11 [95% CI 0.76-1.64]; P=0.58). A statistically significant interaction between continuous BCI(H/I) and treatment was demonstrated (P = 0.036) adjusted for age, tumor size and grade, whereas no significant interaction was observed between treatment and quantitative ER (P=0.939) or PR (P=0.138) expression. Conclusion: BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 vs. 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, for BCI as a predictive biomarker of benefit from extended endocrine therapy. Findings from the Trans-aTTom strengthen the clinical validity of BCI for prediction of endocrine response and its clinical utility in optimizing duration of endocrine therapy. Citation Format: John Bartlett, Dennis Sgori, Kai Treuner, Yi Zhang, Tammy Piper, Ranelle Shalunga, Ikhlaaq Ahmed, Lucy Doos, Sarah Thornber, Elena Brachtel, Sarah Pirrie, Catherine Schnabel, Daniel Rea. Breast Cancer Index predicts benefit from extended endocrine therapy in HR+ breast cancer [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 P2-11-02.
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 | 0,000 | 0,001 |
| 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 | 0,001 | 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) | 0,006 | 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 ».