A biopsy of a tumor lesion (breast or other localisation) will be performed for processing to establish avatars (patient-derived organoids -PDO). 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). 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.

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.

Inclusion Criteria:

1. Patient over 18 years of age
2. Advanced breast cancer
3. Triple-negative phenotype (HR-/HER2-) or HR+/HER2- after hormone resistance (progression after treatment with hormone therapy + CDK4/6 inhibitor)
4. Tumor measurable according to RECISTv1.1 criteria, accessible to biopsy
5. Performans Status 0-1

Exclusion Criteria:

1. More than 3 lines of chemotherapy in the advanced setting (excluding hormone therapy/CDK4/6 inhibitor)
2. Progressive brain metastases
3. Leptomeningeal metastasis

Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accrodance with Institut Curie policies.

Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).