• Signed Informed Consent Form prior to any study-specific procedure. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.

• Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent)

• Male (≥18 years old) or pre-menopausal women (≥40 years old) or post-menopausal women. Premenopausal/male patients will receive LHRH agonists 2 weeks before C1D1 and during treatment. Post-menopausal status is defined as:

‣ Age ≥60 years or

⁃ Age \<60 years and 12 months of amenorrhea plus follicle stimulating hormone (FSH) and plasma estradiol (E2) levels within post-menopausal range by local laboratory assessment or

⁃ Prior bilateral oophorectomy (≥7 days prior to Day 1 of treatment).

• Histologically confirmed invasive breast carcinoma, confirmed by the local pathologist, with all the following characteristics:

‣ Clinical stage II (Seventh Edition of the AJCC) which includes cT1cN1cM0, cT2cN0cM0, cT2cN1cM0 and cT3cN0cM0.

⁃ ER-positive/HER2-negative according to the most recent ASCO/CAP guidelines assessed locally, tumor cells \>10% ER staining, grade 2 or 3 breast cancer.

⁃ Ki-67 index by local analysis of ≥20% on untreated tumor tissue and/or high genomic risk (defined by gene signature): Oncotype DX® RS ≥ 26, Mammaprint® = Risk of Recurrence High, Prosigna® ROR ≥ 60 or luminal B, or Endopredict® = Risk of Recurrence High.

• Note: Multifocal and multicentric tumors are permitted if they are considered clinical stage II according to Seventh Edition of the AJCC. Biopsy of all lesions is not necessary.

• Breast cancer eligible for primary surgery.

• Available pre-treatment FFPE core (tru-cut) biopsy evaluable for PAM50 or possibility to obtain one. Minimal sample requirements are to have at least 1 tumor cylinder with a minimal tissue surface of 4 mm2 tissue, containing at least 10% tumor cells and having enough tissue to do at least 2 cuts of 10 μm each (the quality of the sample must be approved centrally prior to inclusion).

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the date of enrolment.

• Adequate hematological, renal and hepatic function, as follows:

‣ Absolute neutrophil count (ANC) ≥1.5 x 109/L

⁃ Platelet count ≥100 x 109/L

⁃ Hemoglobin ≥10 g/dL

⁃ Alkaline phosphatase (AP) ≤2.5x upper limit of normal (ULN)

⁃ Total bilirubin \<ULN. Patients with known Gilbert syndrome may be enrolled with total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN.

⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5x ULN

⁃ Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/min (Cockcroft-Gault Equation)

⁃ Potassium, total calcium (corrected for serum albumin), magnesium, and sodium within institutional normal limits or corrected to within normal limits with supplements before first dose of study medication.

• Male participants:

• A male participant must agree to use a contraception as detailed in Appendix 1 of this protocol during the adjuvant chemotherapy period (only non-responder cohort) and for at least 21 days, corresponding to time needed to eliminate any study treatments plus an additional 120 days (a spermatogenesis cycle) after the last dose of chemotherapy and refrain from donating sperm during this period. After the end of trial treatment, patients should use effective contraception according to local guidelines.

• Female participants:

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies (see Appendix 1):

‣ Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR

⁃ A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 during the treatment period and for at least 21 days (corresponding to time needed to eliminate any study treatments) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment. After the end of trial treatment, patients should use effective contraception according to local guidelines.