This is a monocentric cohort study, prospective and interventional with minimal risks and constraints for advanced breast cancer. The planned interventions are collection of biological samples at different times. The study will aim to do a descriptive analysis of omics profiles evolution (tumor, volatile organic components) over time, before and after disease progression under Palbociclib treatment with a clinical-biological database.

Patients enrolled in the study will receive the following interventions:

• Biospecimen sample collection: before and during treatment, and at progression
• Tumor biopsy before treatment and at progression

The aim of this study is to describe molecular changes associated with resistance to Palbociclib at the individual level and describe longitudinal changes in the profile of tumor, VOCs and exosomes according to treatment response.

Other objectives of the study include:

• Proportion of single or shared molecular alterations / signatures between patients at progression time
• Associations between tumor signatures, VOCs and exosomes
• Compare molecular changes identified by proteomics with those observed by genomics / transcriptomics
• Compare the evolution of VOCs and exosomes over time with evolution of liquid biopsy markers.

Inclusion Criteria:

• Women over 18 years old
• With histologically proven breast cancer, positives hormones receptors and negative HER2
• Advanced disease (metastases or non-resequable locoregional disease), from the 1st to the 4th line.
• With an indication for hormone therapy associated with the CDK4/6 inhibitor Palbociclib
• Agree to the sampling of the study
• Signed the informed consent form

Exclusion Criteria:

• Neoadjuvant or adjuvant treatment for localized breast cancer
• Metastatic breast cancer beyond the forth line
• Impossibility to give informed consent (person deprived of liberty or under guardianship)

Female with breast cancer