Efficacy of Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women

Inclusion criteria

• Aged ≥ 18 years, Post-menopausal women
• 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)
• Stage II-IIIA
• Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
• Non metastatic, M0
• ER-positive by IHC (Allred Score≥4)
• HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish
• Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation
• ECOG 0-1
• No prior systemic therapy for the present tumor
• 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
• 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.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
• Signed informed consent and health insurance coverage

Exclusion criteria

• Non operable, bilateral, T4 or metastatic breast cancer
• Limited T2 breast cancer immediately accessible to conservative surgery
• 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
• Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
• Previous use of SERMs such as raloxifene
• 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.
• 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
• History of any previous anti-cancer chemotherapy and any previous treatment using AI
• Concurrent administration of herbal preparations as complementary medicine.
• 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
• 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.