The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. In line with the most recent recommendations on targeted anticancer therapies, the investigators have designed a parallel phase II randomized trial with early stopping rules 26, which will able in the meantime to build a unique prospective collection of tumor tissue, pre- and post-treatment.

Inclusion Criteria:

1. Aged ≥ 18 years, Post-menopausal women

2. Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation - Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)

3. Stage II-IIIA

4. Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)

5. Non metastatic, M0

6. ER-positive by IHC (Allred Score≥4)

7. HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish

8. Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation

9. ECOG 0-1

10. No prior systemic therapy for the present tumor

11. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:

    • Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L
    • Platelets ≥100,000/mm3 or ≥100 x 109/L
    • Hemoglobin ≥9 g/dL
    • Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤2.5 x upper limit of normal (ULN)
    • Alkaline phosphatase ≤2.5 x ULN
    • Total serum bilirubin ≤1 x ULN
    • Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution

12. Adequate cardiac functions, including:

    • 12 Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.
    • QTc interval ≤480 msec
    • No history of Torsades de Pointes or other symptomatic QTc abnormality.

13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures

14. Signed informed consent and health insurance coverage

Exclusion Criteria:

1. Non operable, bilateral, T4 or metastatic breast cancer
2. Limited T2 breast cancer immediately accessible to conservative surgery
3. Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
4. Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
5. Previous use of SERMs such as raloxifene
6. Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 4 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures.
7. Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
8. History of any previous anti-cancer chemotherapy and any previous treatment using AI
9. Concurrent administration of herbal preparations as complementary medicine.
10. Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs, such as the inability to take oral medication in tablet form and malabsorption syndrome
11. Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.