Randomized Phase II Study to Assess PD 0332991 in Breast Cancer

Inclusion criteria

• Signed written informed consent
• Female patients aged 18 years or older.
• Histologically or cytologically confirmed untreated invasive carcinoma of the breast irrespective of HER2 and ER status
• No personal history of breast cancer within the last 5 years
• Candidates for initial breast surgery, with a minimum size of 15 mm measured by breast US. Bilateral and multifocal tumors are allowed, assuming tumor evaluations and pre- and post-treatment biopsies are performed in the same target lesion.

• High proliferative tumor as defined by either Grade 3 or Ki67 ≥20% 8. No evidence of metastatic disease. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0/1. 10. Left ventricular ejection fraction (LVEF) of at least 50% 11. Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).

• For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-treatment.

• Patients must be affiliated to a social security system

Exclusion criteria

• Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy or hormonotherapy.
• Patients with previously treated breast cancer during the last 5 years or receiving another concomitant anticancer treatment like chemotherapy, immunotherapy, endocrine

• Known hypersensibility to PD0332991 or any of its components. 5. Difficulty to swallow oral medication 6. Serious uncontrolled concomitant disease that would put the patient at high risk for treatment-related complications.

• Patient whose general clinical condition does not consider postponing surgery 8. Inadequate organ function, evidenced by the following laboratory results:

• Absolute neutrophil count <1,500 cells/mm3
• Platelet count <100,000 cells/mm3
• Hemoglobin <9 g/dL
• Total bilirubin greater than 1,5 times the upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome)
• Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2.5 x ULN
• Serum creatinine >2.0 mg/dL and/or 177 μmol/L clearance creatinine <50mL/min (calculated by Cockcroft-Gault method)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 x ULN (unless on therapeutic coagulation) 9. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.

• Patients with a history of long-QT syndrome or documented family history of long-QT syndrome.

• QTc >470 12. serum potassium level < LLN 13. Uncontrolled intercurrent illness including but not limited to, known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus or psychiatric illness/social situations that would limit compliance with study requirements.

• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

• Pregnant or breastfeeding patients