Abstract P2-11-26: The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor
Notice bibliographique
Résumé
Abstract Background The presence of residual tumour at surgery (non-pathological complete response or non-pCR) occurs in about half of TNBCs treated with neoadjuvant chemotherapy (NAC) and signals chemoresistance and poor prognosis. Although further adjuvant chemotherapy (Capecitabine/Xeloda) results in improved survival in patients with non-pCR, only about 15% of such patients do benefit. Circulating tumor DNA (ctDNA) is a plasma-based biomarker that can be used to reveal real-time data about the disease and treatment progression. We have previously shown that detection of ctDNA after NAC signals poor prognosis. To validate and extend our previous results using an academic hospital-based tumor bespoke assay, we performed ctDNA measurements in non-pCR TNBC patients at the pre-operative, post-operative, 3 and 6-month time points. Methods Whole exome sequencing (WES) was performed on residual tumors from 34 TNBC patients to identify tumour-specific mutations (5/patient). Digital droplet PCR (ddPCR) assays were developed for these mutations and performed as per our previous work. Patients with at least one detectable mutation were considered ctDNA positive for a given time point. The detection of ctDNA was correlated with relapse-free survival (RFS). Results The overall RFS was 44%, with 56 % of patients received adjuvant Xeloda. Detection of ctDNA at the end of NAC (T1) correlated with poor prognosis of RFS (n = 33, p-value = 0.009, HR = 0.29 (95% CI = 0.12 to 0.74)). Detection of ctDNA after surgery (T2) and while on Xeloda (T3) showed no significant prognostic value for RFS. However, ctDNA detection at the 6-month time point, after Xeloda treatment (T4), showed stronger prognostic value for RFS (n = 17, p-value = 0.004, HR = 0.12 (95% CI = 0.03 to 0.51)). When measuring changes in ctDNA detectability from T1 to T4, 4 patients initially positive became ctDNA negative after the 6-month interval, and only 1 of these 4 had a relapse, compared with 10 of 11 that remained positive at the 6-month time point (p = 0.01, Chi-squared test). 3 of the 4 patients that cleared their ctDNA had received Xeloda. In addition, 2 patients initially negative became ctDNA positive at the 6-month time point (T4) and both relapsed, compared with only 1 of 5 that remained negative at 6 months (p = 0.035, Chi-squared test). For patients who received adjuvant Xeloda ctDNA positivity at T1 was associated with a worse RFS (p-value = 0.028, HR = 3.3884 (95% CI = 1.160 to 13.00)). Conclusion ctDNA testing using ddPCR in an academic hospital-based context at the post-NAC time point as well as at 6 months after surgery identifies an excellent prognostic group in TNBC patients with non-pCR and changes in ctDNA during the adjuvant period have prognostic value. This personalized approach to treatment management is ready for prospective testing in patients who have undergone NAC and require additional chemotherapy. Citation Format: Talia Roseshter, Anna Klemantovich, Luca Cavallone, Adriana Aguilar-Mahecha, Josiane Lafleur, Oluwadara O. Elebute, Sarah Jenna, Jean-Francois Boileau, Manuela Pelmus, Mark Basik, Cathy Lan. The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-26.
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 | 0,000 |
| 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) | 0,002 | 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 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 ».