Abstract TC1-3-1: Ki 67 Ki67 – a clinically relevant biomarker or just <i>nice to have</i> information?
Notice bibliographique
Résumé
Abstract Ki67 is an immunohistochemical marker indicating the growth fraction of cycling cells from G1 to S-phase in tumor specimens. In breast cancer, Ki67 is a prognostic marker with high values indicating poor outcome. Over the last decades, obstacles for its wide-spread use in clinical practice included lack of methodological standardization and lack of specific cut-off values for clinical decision making, i.e. discrimination of luminal A vs. B early breast cancer (EBC), chemotherapy indication in HR+/HER2- EBC. However, recently, the International Ki67 working group has put forward consensus statements for a standardized methodology. In general, reproducibility of Ki67 values at extreme sides of the spectrum such as 10% or ≥ 35% is much higher than in the intermediate range and quality assurance programs substantially improve laboratory performance. Moreover, clinical utility has also become apparent in two specific settings of HR±/HER2- EBC. First, the monarchE trial evaluating adjuvant abemaciclib in node-positive high-risk disease used a Ki67 cut-off of 20% as a criterion for aggressive disease and as a sole inclusion criterion for patients with 1-3 lymph nodes (cohort2). While data for this cohort have not yet been reported, Ki67 was a strong prognostic factor in the overall trial population with patients with high Ki67 having worse outcome than those with Ki67 < 20%. Benefit from abemaciclib was independent of Ki67 index. Nevertheless, some health authorities included Ki67 in their abemaciclib label as the absolute benefit was greater in tumors with Ki67 ≥ 20%. Second, Ki67 response after a short (2-4 week) preoperative endocrine therapy allows endocrine response assessment by determining Ki67 in the surgical specimen. This information is widely used in drug development. Ki67post 10% has been defined as endocrine response. In the POETIC trial, endocrine response was associated with improved outcome compared to tumors with Ki67 ≥ 10% after 2-weeks of preoperative AI in postmenopausal patients. In the WSG ADAPT trial, patients with 0-3 lymph nodes, Recurrence Score 25 and endocrine response had excellent outcome with adjuvant endocrine therapy alone independent of menopausal status (5-year dDFS ≥ 95%). In postmenopausal women, probability of endocrine response with an AI is around 80% whereas in premenopausal patients with tamoxifen it is only around 40%. Yet, in premenopausal women addition of GnRH substantially improves endocrine response probability reaching about 80% with GnRH and AI as recently shown by interim analysis of the WSG ADAPTcycle trial (about 2500 patients). Endocrine response probabilities seen in the ADAPT trial (≥ 5000 patients) were validated in ADAPTcycle demonstrating clinical validity of this biomarker. In conclusion, Ki67 is a clinically relevant biomarker that can be used for clinical decision making, particularly in HR+/HER2- EBC. As there is no single generally accepted Ki67 cut-off value to discriminate prognostically favorable from aggressive EBC, Ki67 needs to be used in the context of tumor burden and tumor biology. Currently, next to its use in allocating patients to adjuvant abemaciclib in countries where Ki67 index is included in the label, it provides clinically important information after short-term preoperative endocrine therapy regarding endocrine response in HR+/HER2 EBC. Given its easy and inexpensive determination method, its analytical validity within quality assurance programs, and its clinical usefulness, Ki67 needs to be integrated in our biomarker portfolio in EBC. Citation Format: Nadia Harbeck, Torsten Nielson. Ki 67 Ki67 – a clinically relevant biomarker or just nice to have information? [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 TC1-3-1.
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 | 0,006 | 0,035 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,006 | 0,004 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,004 | 0,006 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,032 | 0,022 |
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 ».