Efficacy of Personalized Tumorogram-based Therapy in Cancer Established From Patient-derived Organoid (AVATAR)

A biopsy of a tumor lesion (breast or other localisation) will be performed and transferred to the LIP laboratory at the Institut Curie (Laboratoire d'Investigation Préclinique, Département de Recherche Translationnelle) for processing to establish avatars (patient-derived organoids -PDO).

Step 1: Establishment of avatar (PDO): follow-up of line N (standard care) when the tumorogram is established, then follow-up of standard line N+1.

* The patient will then be treated (line N) as part of standard care while awaiting the result of the tumorogram. * A drug screening will be carried out on the PDO (\~5-10 drugs/patient), which will be progressive and adapted to the clinical context (including treatment history), including drugs used in standard care (cf. list in Table 1). * A personalized tumorogram for each patient will be provided, based on the results of the drug screening (= tumor predicted as sensitive, intermediate, resistant or non-evaluable for each drug tested). * A multidisciplinary committee will be set up for this study, which will meet regularly (\~1 time per week) to discuss patients included in the study, obtaining PDOs, drugs to be prioritized in the screening, results of the drug screening and personalized tumorograms. The committee will include at least one oncologist and one biologist from the laboratory. * The multidisciplinary committee will make a therapeutic recommendation based on the personalized tumorogram, which may include several drugs considered sensitive to the tumour * A tumorogram will be considered as informative if it proposes at least one chemotherapy molecule considered as sensitive in the PDO model. * Patients whose PDO could not be obtained, or whose tumorogram was not informative, will receive standard treatment.

Step 2: informative tumorogram: follow-up of experimental line N+1 Patients with an informative tumorogram will receive one of the recommended treatments (line N+1) in the event of tumor progression, administered according to standard procedures and validated at medical meetings specific to each center, and their fate will be monitored.

• Comparison of response rate between both the arms [Time frame: 6 months]
• Organoid cultures achievement [Time frame: 6 months]
• Tumorograms performance [Time frame: 6 months]
• Overall survival [Time frame: up to 18 months]