RATIONALE : Currently, the mechanisms associated with the response or resistance to treatment are poorly understood and are multifactorial. These mechanisms involve clinical and biological factors associated with the host and the tumor and possibly the patient's psycho-social environment.

PURPOSE : This trial will assess the use of a prospective database dedicated to patients with breast cancers that contains clinical data as well as epidemiological, psychological, emotional, social, imaging, biological and bio-pathological data. These data will allow a creation of new modelling algorithms in order to predict response and resistance to treatment.

This prospective study will be conducted on first line metastatic breast cancer patients.

Three phenotypic groups are identified on immunohistochemistry done at inclusion: on metastatic sites or breast tumor if local recurrence, usual treatment protocols are often guided by the following groups:

• Group 1 : Patients HR (Hormon Receptor) + (E (Estrogen Receptor) + and/or PR (Progesterone Receptor) +) and HER2- (Human Epidermal Growth Factor Receptor-2)
• Group 2 : Patients HER2 + with or without HR+
• Group 3 : Patients triple negative (HR- and HER2-) Patients will receive treatments as per standard care according to the patient group.

Standard treatments recommended for treatment first line are:

1. For group 1 : For HR + and HER2- patients :

   • For patients requiring Chemotherapy (visceral crisis), the recommended treatment is : Taxanes based chemotherapy Anthracyclines based chemotherapy
   • For the patients without visceral crisis: the recommended treatment is : Hormonal therapy combined with CDK 4-6 inhibitors (Cyclin-dependent kinase) as recommended in standard care.

2. For group 2 : HER2 + (with or without HR+), the recommended treatment is :

   • Paclitaxel (Taxol) combined with Trastuzumab (Herceptin) and Pertuzumab (Perjeta) as per the institutional standard of care.
   • Docetaxel (Taxotere) combined with Trastuzumab (Herceptin) and Pertuzumab (Perjeta) as per the institutional standard of care.

3. For group 3 : triple negative (HR- and HER2-) patients, the recommended treatment is :

   • Paclitaxel (Taxol) with or without Bevacizumab (Avastin) as per the institutional standard of care.

Further treatment lines are administered according to standard practice. Biological and histological assessments are performed on specific metastasis biopsy samples done at baseline and at each progression.

Physical exam, standard laboratory tests, imaging (CT (computerized tomography) scan, PET-CT (Positron emission tomography-computed tomography) and bone scan (for patients with bone metastasis) will be performed every 2 to 6 months according to patient group.

Clinical, biological, pathological, epidemiological, socio-economic and multi-omic data will be collected throughout the study duration.

These massive data will be used to create new algorithms in order to help clinicians to predict treatment response.

Inclusion Criteria:

1. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening biopsy, blood sample, faeces and questionnaires

2. Women > 18 years old at time of written consent

3. Patient with histologically confirmed breast cancer

4. Breast cancer metastatic disease or locally advanced not eligible for local curative treatment intent with or without personal history of adjuvant therapy for this cancer (chemotherapy, radiotherapy, surgery …)

5. Patient with metastases that can be biopsied.

6. Performance status ≤ 2 (according to WHO criteria)

7. Indication of any systemic therapeutic strategy can be performed alongside this current cohort in accordance with national and / or international recommendations.

8. HR and HER2 status on metastatic sites or breast tumor if local recurrence:

   • For group 1 :

     • Histologic and/or cytological confirmation of estrogen-receptor positive (ER+) and/ or progesterone receptor positive (PR+) breast cancer determined by local laboratory testing
     • No HER2-overexpression in the patient's tumor tissue determined by local laboratory testing

   • For group 2 :

     • Histologic and/or cytological confirmation of estrogen-receptor positive or negative and/ or progesterone receptor positive or negative breast cancer determined by local laboratory testing
     • HER2-overexpression in the patient's tumor tissue determined by local laboratory testing

   • For group 3 :

     • Histologic and/or cytological confirmation of estrogen-receptor negative and progesterone receptor negative breast cancer determined by local laboratory testing
     • No HER2-overexpression in the patient's tumor tissue determined by local laboratory testing

9. Menopausal status : as per the institutional standard of care

10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

11. Patient must be affiliated to a Social Health Insurance

Exclusion Criteria:

1. Other malignancy treated within the last 5 years (except non-melanoma skin cancer or in situ carcinoma of the cervix)
2. Coagulopathy or other pathology that contraindicates biopsy procedures
3. Prior systemic treatment in metastatic setting
4. Patients with exclusive brain metastasis not available for surgery
5. Pregnant or nursing patient
6. Individual deprived of liberty or placed under the authority of a tutor
7. Impossibility to submit to the medical follow-up of this clinical trial for geographical, social or psychological reasons