Characterization of molecular response and progression in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors using a high-sensitivity tumor-informed assay.
Notice bibliographique
Résumé
3052 Background: Tumor-informed circulating tumor DNA (ctDNA) assays, designed to track patient (pt) specific variants identified by tumor sequencing, offer enhanced sensitivity compared to traditional assays focused on driver genes. This approach enables precise ctDNA quantification, facilitating early detection of molecular progression and innovative strategies in metastatic breast cancer (mBC). Methods: HR+/HER2- mBC pts receiving standard endocrine therapy + CDK4/6 inhibitors (CDKi) were enrolled in a prospective observational cohort (2018–2023). Plasma samples were collected at baseline (BL), within 30 days (d) and ~q3 months with restaging scans. Archival tumor WES was used to design personalized panels for ctDNA monitoring. The primary endpoint was time to treatment failure (TTF). Results: Of 51 pts analyzed (median age 60 years [range 38-88], 1/2L [75/20%], visceral disease 63%, palbo-/ribo-/abemaciclib 76/22/2%), tumor-informed panels were successfully designed for 43 (1 failed WES, 7 failed QC), detecting BL ctDNA in 39 (91%). The median BL estimated variant allele fraction (eVAF) was 0.5% (0.006–17.9) and was associated with liver metastases but no other covariates (e.g. bone-only disease, history of 1ry endocrine resistance [ER]). Higher BL eVAF predicted shorter TTF (HR 1.14 CI 95% 1.05–1.23, p<0.01). Most pts had eVAF decreases below BL in the first 30 d (78%) and before the first scan (89%; median 90 d, 23–158). Early increases above BL did not significantly predict TTF, with 3/8 cases showing prolonged responses. ctDNA clearance was observed in 11/39 (28%) pts at a median of 172 d (14–410) and predicted longer TTF (HR 0.06, CI 95% 0.01–0.45, p<0.01; median TTF not reached vs 14.5 mo for pts with and without clearance), with treatment failure (TF) rates of 0% vs 40%, and 8% vs 80%, at the 1- and 2-year landmarks, respectively. Clearance was not associated with any clinical covariate (i.e. disease sites, therapy line, CDKi, history of 1ry ER). For any sample irrespective of the trajectory, higher eVAF ratios to BL predicted shorter lead times to TF, though with poor correlation (r 2 0.08, p=0.01). eVAF ratios to BL >1, >0.5 and <0.5 at any timepoint had median lead times to TF of 76 d (Q1–Q3 25–135), 133 d (41–360), and 326 d (174–471). A complete analysis of ctDNA dynamics and operating parameters will be presented along with RECIST 1.1 evaluation and WES-based genomic subgroups. Conclusions: ctDNA levels and changes on therapy are prognostic and high sensitivity tumor-informed assays expand the proportion of pts who can be monitored. ctDNA clearance identified pts with better outcome and might inform pt follow up and interventional strategies. Reappraisal of existing early response cutoffs, with limited precision for individual decision making, may be necessary with more sensitive assays.
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 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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 ».