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
