Biomarkers in Patients With Metastatic Breast Cancer

Procedure: 1. Verification of the inclusion / non-inclusion criteria 2. Signing the consent form 3. Surgical, Medical and family history, ongoing treatments 4. Clinical Examination1 5. Radiological examinations 2 6. TNM Classification (Appendix 3) 7. Standard biochemical assessment 3 8. Inflammatory assessment (CRP, LDH, IL6) 9. Hematological assessment (NFS, platelets) 10. Tumor markers (ACE, CA15-3) 11. Histological and molecular examination 4: * Expression PD-L1 by IHC (Immuno-Histochemistry) * TILs by IHC * \- MSI status: MMR \* proteins (Mismatch Repair Protein) (Appendix 4) by NGS via TruSight™ Oncology 500 Kit (Illumina) , if PD-L1\>1% * Score HRD : by NGS via TruSight™ Oncology 500 Kit (Illumina) , if PD-L1\>1% * TMB mutational burden by next generation sequencing "Next Generation Sequencing" (NGS) via TruSight™ Oncology 500 Kit (Illumina) if PD-L1\>1% * tDNA by digital PCR 12. Radiological evaluation5 13. Indication of surgery? (if yes type of surgery to be specified) 14. Evaluation of adverse events / effects: Tolerance of the previous treatment 15. Completion the source documents and the eCRF Clinical Exam1: * General State according to the WHO classification or according to the Karnowsky Index * Breast examination: inspection (symmetry, appearance of the skin), palpation (size of the tumor, presence of mammary discharge). * Examination of the axillary and supraclavicular lymph node areas * Abdominal examination * Pulmonary auscultation * Skeleton examination Radiological examination2: * Mammography and echo-mammary * Thoraco-abdomino-pelvic CT scan * Bone scintigraphy * Cardiac ultrasound Standard biochemical balance3: Blood group, creatininemia, blood ionogram, calcemia, glycemia, bilirubin, transaminases, gamma-GT, alkaline phosphatases, total cholesterol, triglycerides, uric acid, albuminemia. Histological examination4: * Biopsy with part number assigned by the laboratory, name of the laboratory * Histological type * Grade of Scarff-Bloom and Richardson (SBR) * Estrogen receptors, progesterone receptors * Her2Neu * Ki67 * PD-L1 * TILs * MMR Molecular Examination4: * MSI status by pentaplex PCR and capillary electrophoresis by NGS platform via the TruSight™ kit Oncology 500 (Illumina) * HRD Score by NGS platform via the TruSight™ kit Oncology 500 (Illumina) * Mutational burden TMB by NGS platform via the TruSight™ kit Oncology 500 (Illumina) * Circulating tumor DNA by digital PCR Radiological assessment5: * If the stage is locally advanced (appendix 3): Breast ultrasound +/- Mammography +/- Breast MRI * If metastatic stage: Thoraco-abdomino-pelvic CT scan 12 \| 27 Visit details • Initial visit D0 (V1) * Signature of informed consent form * Verification of inclusion / non-inclusion criteria * Medical, surgical and family history * Current treatments * Clinical examination1 * Radiological examinations2 * TNM classification * Standard biochemical assessment3 * Inflammatory assessment (CRP, LDH, IL6) * Hematological assessment (NFS, platelets) * Tumor markers (ACE, CA15-3) * Histological examination with immunohistochemistry and molecular4: * Biopsy with part number assigned by the lab, name of the lab * Histological type * SBR grade * Estrogen receptors, progesterone receptors * Her2Neu * Ki67 * PD-L1 * TILs * MMR * MSI * HRD * TMB mutational charge * ctDNA o Completion of source documents and eCRF * Visit after 3 chemotherapy treatment cycles (V2) * Current treatments * Clinical examination1 * Hematological assessment (NFS, platelets) * Tumor markers (ACE, CA15-3) * Radiological assessment5 * Evaluation of adverse events / effects: Tolerance of the previous treatment * Completion of source documents and eCRF * Assessment visit (V3) o Current treatments o Clinical examination1 * TNM classification * Inflammatory assessment (CRP, LDH, IL6) * Hematological assessment (NFS, platelets) * Tumor markers (ACE, CA15-3) * Histological examination with immunohistochemistry and molecular4: * Biopsy with part number assigned by the lab, name of the lab * Histological type * SBR grade 13 \| 27 * Estrogen receptors, progesterone receptors * Her2Neu * Ki67 * PD-L1 * TILs * ctDNA o Radiological assessment5 o Assessment of adverse events / effects o Fill in the source files and the eCRF * Follow-up visit at 3 months (V4) o Current treatments o Clinical examination1 o Tumor markers (ACE, CA15-3) o Radiological examinations2 o Evaluation of adverse events / effects * Completion of source documents and eCRF * Follow-up visit at 6 months (V5) o Current treatments o Clinical examination1 o Tumor markers (ACE, CA15-3) * Radiological examinations2 * Evaluation of adverse events / effects * Completion of source documents and eCRF