A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)

Exclusion Criteria

• •Patient has received any prior therapy for breast cancer.
• •Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• •Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
• •* History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
• •* History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• •* Documented cardiomyopathy
• •* Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• •* History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, Long QT Syndrome or conduction abnormality in the previous 12 months.
• •* Family history of QTc prolongation or of unexplainable sudden death at \<50 years of age.
• •* On screening 12 lead ECG, any of the following cardiac parameters: bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \>109 msec, or QTcF \>450 msec.
• •* Systolic blood pressure \>160 mmHg or \<90 mmHg.
• •Patient is currently receiving any of the following medications (see
• •Appendix 1 for details):
• •That are known strong inducers or inhibitors of CYP3A4.
• •That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.
• •That have a known risk to prolong the QT interval or induce Torsades de Pointes.