Abemaciclib and SRS for Brain Metastases from Breast Cancer

Inclusion Criteria: * HR+ breast cancer to fulfill the requirement of HR+ disease, a breast cancer must express (≥ 1%), by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor \[ER\] or progesterone receptor \[PR\]) as defined in the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Guidelines * To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines * ≤ 15 brain metastases eligible for stereotactic radiation * Able to swallow oral medications * Willing to comply with all study procedures and available for duration of the study * Measurable brain disease per RANO-BM criteria that can be measured in at least one dimension as ≥ 0.5 cm for both intact brain metastases and post-operative cavities * Eligible for SRS to brain metastases or to the post-operative bed following surgical resection * Maximum diameter of the largest intact brain metastases ≤ 4 cm * Eastern Cooperative Oncology Group performance status 0 to 2 * A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. If attempts to obtain archival tissue are unsuccessful the patient may be enrolled. * Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will be allowed if active measurable disease has not previously been treated with radiation therapy * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 7 days of the first dose of abemaciclib * WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s), and for three weeks following the last dose of abemaciclib * Adequate organ function as defined in protocol Exclusion Criteria: * Presence of leptomeningeal disease * Prior receipt of whole brain radiation therapy * Prior receipt of abemaciclib in the setting of brain metastases or in the past 6 months for the treatment of metastatic disease. * All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) other than: a. Toxicities attributed to prior anticancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy b. Toxicities that are not expected to interfere with study treatment, such as fatigue, alopecia, or grade 2 hematologic toxicity * Women who are pregnant or breastfeeding * The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) * The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment * The patient has a 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 * History of prior malignancy within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of \>90%), such as but not limited to, non-melanoma skin carcinoma, or stage I endometriod uterine cancer, and others at the discretion of the PI. * Major surgery or significant traumatic injury that has not been recovered from by 14 days before the initiation of study drug * Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of first dose of study treatment * History of allergy or hypersensitivity to any of the study drugs or study drug components * Prisoners or individuals who are involuntarily incarcerated