RADIANT: Pre-op Radiation With Abemaciclib and Letrozole

Eligibility 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:
• * HR positive/HER2 -negative breast cancers are allowed as long as no other exclusions exist
• * 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