Inclusion Criteria:

          1. Women with newly diagnosed and histologically proven de novo adenocarcinoma of the
             breast, Any T, any N, with at least one metastatic site measurable and/or
             non-measurable according to Response Evaluation Criteria In Solid Tumours (RECIST)
             v1.1 and/or PET Response Criteria in Solid Tumours (PERCIST) v1.0 and/or MD Anderson
             bone response criteria (MDA criteria). For patients with only bone metastases, at
             least one lytic and non-irradiated lesion must be present NB: Bilateral breast cancer
             is allowed only if tumours present similar histological criteria (morphological
             subtype, ER and HER2 status).

          2. Estrogen Receptor (ER)-positive and HER2-negative breast cancer. To be considered as
             ER-positive, the biopsy of the primary tumour must display at least 10% of cancer
             cells with positive ER staining. HER2-positive is defined as IHC3+ or FISH/CISH
             amplified according to 2018 criteria

          3. Age ≥18 years

          4. Eastern Cooperative Oncology Group (ECOG) ≤2

          5. Indication for treatment with palbociclib and letrozole (with or without ovarian
             suppression)

          6. Diagnostic FFPE tumour sample and/or frozen primary breast tumour sample available

          7. Women of childbearing potential must have a negative serum or urine pregnancy test
             done within 14 days before inclusion

          8. Patients must agree to use adequate contraception methods for the duration of the
             study and for within 21 days after completing treatment

          9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and any protocol-related procedures including absence of co-morbidities
             preventing surgery and or radiotherapy and any psychological, familial, sociological
             or geographical condition potentially hampering compliance with the study protocol and
             follow-up schedule. Those conditions should be discussed with the patient before
             registration in the trial

         10. Patient affiliated to a social security system

         11. Written informed consent obtained prior to performing any protocol-related procedures
             including screening evaluations

        Exclusion Criteria:

          1. Patients with advanced, symptomatic, visceral spread at a risk for short-term,
             life-threatening complications according to investigator judgement and at risk for
             visceral crisis as defined by ABC4*

          2. Women with previously diagnosed and treated ipsilateral adenocarcinoma of the breast

          3. Women with previously treated or concomitant contralateral breast cancer except for
             Ductal carcinoma in situ (DCIS) treated with curative intent

          4. Patients with another concomitant cancer

          5. Concurrent enrolment in another clinical trial in which investigational therapies are
             administered or administration of an investigational drug within 30 days before
             inclusion

          6. Pregnant women or women who are breast-feeding

          7. Inability or willingness to swallow oral medication

          8. HIV, hepatitis (B and C)

          9. Active infection

         10. Prior therapy for metastatic breast cancer (systemic or local)

         11. Persons deprived of their freedom or under guardianship or incapable of giving consent

               -  Visceral crisis is defined as severe organ dysfunction as assessed by signs and
                  symptoms, laboratory studies and rapid progression of disease. Visceral crisis is
                  not the mere presence of visceral metastases but implies important visceral
                  compromise leading to a clinical indication for a more rapidly efficacious
                  therapy, particularly since another treatment option at progression will probably
                  not be possible.