biomarkers in patients with metastatic breast cancer

Conditions: Identify the Number of Eligible Patients for Immunotherapy According to the Epidemiological and Biological Profile in Tunisia

Summary: in order to allow tunisian patients with breast cancer to access immunotherapies, and innovative treatments to extend life expectancy of patients with breast cancer with a poor prognosis, it is important to study the epidemiological profile of tunisian cancers breast, in terms of pd-l1 expression, tumor mutational burden (tmb), microsatellite instability status (msi) and rate of tils, in metastatic and locally advanced cases, in tunis, over a one-year follow-up period. it is also important to study other inflammatory and tumor biomarkers which would have a prognostic or even therapeutic value: * serum dosage of ldh (lactate dehydrogenase) * il-6 (interleukin 6) * crp (c-reactive protein) * absolute count of lymphocytes (cla) and eosinophils * quantification of circulating tumor dna before treatment and under treatment. the primary objective id to identify the epidemiological profile of the biological signature (pd-l1 / tmb / msi/hrd/ tils) of patients with locally advanced or metastatic breast carcinoma before and during the systemic treatment.

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

Eligibility criteria:
inclusion criteria: * age ≥ 18 years old. * signed informed consent * histological evidence of breast carcinoma. * locally advanced (stage iii inoperable) or metastatic (stage iv) carcinoma, the metastases of which have been diagnosed straight away or after adjuvant or neoadjuvant treatment. * no treatment for metastatic disease. * metastatic disease: histological evidence of metastasis * patients who will receive systemic treatment (chemotherapy, targeted therapy, hormone therapy) * life expectancy greater than 3 months exclusion criteria: * non-epithelial breast cancer * non-biopsiable metastases * patients who have received before systemic treatment for metastatic disease (chemotherapy, targeted therapy, hormone therapy) * patients with a contraindication to chemotherapy, and / or hormone therapy, and / or targeted therapy. * foreign patients