A Phase III Randomized, Double-Blind, Neoadjuvant Study of Hormonal Therapy plus Palbociclib versus Hormonal Therapy plus Placebo in Women with Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

INTERVENTION: Intervention type:DRUG. Intervention1:hormonal therapy plus palbociclib, Dose form:CAPSULE, Route of administration:ORAL, intended dose regimen:Palbociclib Treatment Palbociclib will be administered orally once a day for 21 days of every 28 day cycle followed by 7 days off treatment. Starting dose: 125mg, Reduction dose level 1: 100mg, Reduction dose level 2: 75mg, Hormonal Treatment Pre‐ and peri‐menopausal women will be receiving Ovarian Function Suppression (OFS) by either leuprorelin subcutaneous 3.75 mg q28days or goserelin subcutaneous 3.6 mg q28days plus tamoxifen 20 mg QD in 28‐day cycles. Post‐menopausal women will receive letrozole 2.5 mg QD in 28‐day cycles.. Control intervention1:hormonal therapy plus palbociclib, Dose form:CAPSULE, Route of administration:ORAL, Intended dose regimen:Placebo Palbociclib will be administered orally once a day for 21 days of every 28 day cycle followed by 7 days off treatment. Starting dose: 125mg, Reduction dose level 1: 100mg, Reduction dose level 2: 75mg, Hormonal Treatment Pre‐ and peri‐menopausal women will be receiving Ovarian Function Suppression (OFS) by either leuprorelin subcutaneous 3.75 mg q28days or goserelin subcutaneous 3.6 mg q28days plus tamoxifen 20 mg QD in 28‐day cycles. Post‐menopausal women will receive letrozole 2.5 mg QD in 28‐day cycles.. CONDITION: In Untreated Women with Operable, HR‐positive and HER2‐negative Breast Cancer PRIMARY OUTCOME: PEPI; EndoPredicTM EPclin Score. Timepoint:PEPI:At screening and surgery; EPclin Score:At surgery . SECONDARY OUTCOME: Clinical Response Rate (CRR); Drop in Ki67 <= 2.7%; Rate of pathological CR (pCR); Breast conserving rate (BCR); Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities. ; Biomarker studies in serum, plasma, urine and tumor tissue. Timepoint: Refer to Other Information . INCLUSION CRITERIA: 1.Pre/peri‐ or post‐menopausal women 18 years and older (or local legal age, whichever is higher) 2.Primary tumor greater than 2 cm in diameter 3.Histologically proven invasive breast cancer 4.Positive hormone receptor (ER and/or PgR >= Allred 3) 5.Negative HER‐2 receptor 6.Ki67 index equal to or greater than 14% (Ki67 >= 14%) by centr 7.Eastern Cooperative Oncology Group Performance Status (ECOG PS) <= 1 or Karnofsky performance status >= 70% 8.No previous history of radiotherapy or systemic therapy including chemotherapy and hormone therapy for breast cancer 9.Laboratory values must be as follows: Absolute neutrophil count:>= 1,500/mm3 Platelets: >= 100,000/mm3 Hemoglobin: >= 9 g/dL Bilirubin: <= 1.5 x upper limits of normal (ULN) Serum Creatinine: <= 1.5 x ULN Alkaline phosphatase: <= 2 x ULN Alkaline phosphatase: <= 2 x ULN AST and ALT: <= 2 x ULN Cardiac function: Normal finding of Electrocardiogram (E