RADIANT Study: Phase Ib Study of Pre-op Radiation with Abemaciclib and Letrozole in Early Stage Breast Cancer.

Inclusion Criteria: - Histologically and/or cytologically confirmed diagnosis of invasive (ductal, lobular or mixed histology), Clinically inapparent tumor that is not palpable. (cT1-T2N0)disease. Minimum tumor size of 1.5 cm - Expression of ER or progesterone receptors (PR)and negative expression of HER2 per American Society of Clinical Oncology, (ASCO) Common Alerting Protocol (CAP) guidelines - Oncotype diagnosis (DX) Breast Recurrence score of less than 25 on core biopsy specimen - Post-menopausal status defined: - age <60 with amenorrhea for at least 12 months in the absence of prior chemotherapy, tamoxifen, toremifene, or ovarian suppression and estradiol and FSH (follicle stimulating hormone) in postmenopausal range. - No clinical suspicion of metastasis disease - Eastern Cooperative Oncology Group (ECOG) performance status of follicle stimulating hormone (PFS) ≤2 - Eligible to undergo surgery, either lumpectomy or mastectomy for local treatment of the breast cancer - Able to swallow oral medications - Adequate organ function for all of the following: Absolute Neutrophil (ANC) >1.5 x 10/L Platelets >100 x 10/L Hemoglobin >8 g/dL - May receive erythrocyte transfusions to achieve this level Total Bilirubin <1.5 x Upper Limit of Normal (ULN) Alanine Aminotransferase (ATL) and Aspartate Aminotransferase (AST) <3 x ULN - HR positive/HER2 -negative breast cancers are allowed as long as no other exclusions exist Exclusion Criteria: - History of ipsilateral breast cancer - Prior treatment with CDK4/6 inhibitors or aromatase inhibitors - History of chest wall or ipsilateral breast radiation - Inflammatory breast cancer - Needs neoadjuvant chemotherapy - Presence of distant metastatic disease - Contraindication for surgery - Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg) - Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study - Life expectancy < 12 weeks - History of allergy or hypersensitivity to any of the study drugs - Any significant medical condition, laboratory abnormality, or psychiatric illness - Serious and/or uncontrolled preexisting medical condition - Has had major surgery within 14 days prior to enrollment - Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research - Has active systemic bacterial infection - Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest