Development of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancer.

Purpose The recent publication of the ACOSOG Z1031 trial results demonstrated that Ki-67 proliferation marker-based neoadjuvant endocrine therapy response monitoring could be used for tailoring the use of adjuvant chemotherapy in ER+HER2-negative breast cancer patients. In this paper, we describe the development of the Ki-67 clinical trial assay used for this study.Methods Ki-67 assay assessment focused on reproducing a 2.7% Ki-67 cut-point (CP) required for calculating the Preoperative Endocrine Prognostic Index and a 10% CP for poor endocrine therapy response identification within the first month of neoadjuvant endocrine treatment. Image analysis was assessed to increase the efficiency of the scoring process. Clinical outcome concordance for two independent Ki-67 scores was the primary performance metric.Results Discordant scores led to a triage approach where cases with complex histological features that software algorithms could not resolve were flagged for visual point counting (17%). The final Ki-67 scoring approach was run on T1/2 N0 cases from the P024 and POL trials (N = 58). The percent positive agreement for the 2.7% CP was 87.5% (95% CI 61.7-98.5%); percent negative agreement 88.9% (95% CI: 65.3-98.6%). Minor discordance did not affect the ability to predict similar relapse-free outcomes (Log-Rank P = 0.044 and P = 0.055). The data for the 10% early triage CP in the POL trial were similar (N = 66), the percentage positive agreement was 100%, and percent negative agreement 93.55% (95% CI: 78.58-99.21%). The independent survival predictions were concordant (Log-rank P = 0.0001 and P = 0.01).Conclusions We have developed an efficient and reproducible Ki-67 scoring system that was approved by the Clinical Trials Evaluation Program for NCI-supported neoadjuvant endocrine therapy trials. Using the methodology described here, investigators are able to identify a subgroup of patients with ER+HER2-negative breast cancer that can be safely managed without the need of adjuvant chemotherapy

Tuteurs en ligne : quels rôles, quelle formation ?

Le projet LEARN-NETT (SOCRATES-CE) vise à développer et promovoir l'usage des Nouvelles Technologies dans et pour la formation des enseignants. Dans ce cadre, des groupes composés d'étudiants de différentes universités européennes sont supervisés par des "tuteurs en ligne" qui les aident à communiquer, collaboraer et mener une réflexion autour d'un projet commun. Cette contribution présente et analyse les différents rôles de ces tuteurs et propose un modèle de formation de "tuteur en ligne".The LEARN-NETT project aims at developing and promoting the use of ICT into and for teachers' training. In this way, groups composed by students from different european universities are supported by an "on-line tutor" who helps them to communicate, collaborate and lead a reflection during collaborative project. This contribution presents and analyses the different roles of these tutors and proposes a model for an "on-line tutor" training.Projet LEARN-NETT-SOCRATES (CE