Abemaciclib in Treating Patients with Rb Positive Triple-Negative Breast Cancer That is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed by Surgery

Inclusion Criteria

• Patients must have histologically or cytologically confirmed invasive breast cancer, which is recurrent, locally advanced, unresectable or metastatic
• Patients must have at least one lesion that is not within a previously radiated field and that is measurable per RECIST version 1.1; bone lesions are not considered measurable
• Either the primary tumor and/or metastatic tumor must be triple-negative as defined below: * Hormone receptor status: the invasive tumor must be estrogen receptor (ER)- and progesterone receptor (PR)- negative, or staining present in < 1% by immunohistochemistry (IHC) * HER2 status: the invasive tumor must be human epidermal growth factor receptor 2 negative (HER2-negative) by the American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines * In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, then the triple-negative status of the tumor should be determined from the most recent sample available
• Either the primary tumor and/or the metastatic tumor must be RB positive as defined below: * RB status: the invasive tumor must have greater than 50% of tumor cells staining positive for RB
• Prior chemotherapy: * Patients may have received 1-3 prior therapies for metastatic disease (note: for patients who have first developed recurrent/metastatic disease within 12 months of completing any [neo]-adjuvant therapy for triple-negative breast cancer, the [neo]-adjuvant therapy is counted as a prior line of therapy) * Patients must have been off treatment with myelosuppressive chemotherapy for at least 21 days or nonmyelosuppressive agents for 14 days before registration; patients should also be adequately recovered (to baseline or grade 1) from acute toxicities of prior treatment except for residual alopecia and peripheral neuropathy
• Prior biologic therapy: Patients must have discontinued all biologic therapy at least 21 days before registration
• Patients may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least 7 days prior to study registration
• Patients on bisphosphonates or RANK-L inhibitors may continue receiving these therapies during study treatment; there is no washout period required between the last dose of these therapies and the start of abemaciclib
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 8 g/dL * Note: Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must not begin earlier than the day the after the erythrocyte infusion
• Total Bilirubin =< 1.5 x the upper limit of normal (ULN) or =< 2.0 x the upper limit of normal (ULN) in patients with documented Gilbert’s syndrome
• Serum creatinine =< 1.5 mg/dL OR calculated glomerular filtration rate (GFR) >= 60 mL/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the upper limit of normal; for patients with documented liver metastases, AST/ALT =< 5.0 times the upper limit of normal
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening; women of childbearing potential are defined as those who have not been surgically sterilized and have had a menstrual period in the past year
• Capable of understanding and complying with the protocol and has signed the informed consent document
• Able to swallow study drug
• Sexually active patients (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months after completion of study treatment; if a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately; while on the study and for 3 months after final drug administration, women may not breast-feed
• Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue
• Patients with tumor that is felt to be accessible to biopsy must be willing to provide tissue from a newly obtained core biopsy of a tumor lesion at baseline; biopsies will be obtained up to 1 week (7 days) prior to initiation of treatment on cycle 1, day 1; patients who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol

Exclusion Criteria

• Received a prior CDK4/6 inhibitor
• Undergone major surgery within 14 days of the initial dose of study drug
• Received another investigational agent (defined as any agent/device that has not received regulatory approval for any indication) within 14 days of the first dose of study drug for a nonmyelosuppressive agent, or 21 days of the first dose of study drug for a myelosuppressive agent
• Has any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator
• Has an active bacterial infection (requiring IV antibiotics at the time of initiating study treatment), fungal infection, or detectable viral infection; patients with known human immunodeficiency virus (HIV) infection are excluded given the potential for interactions between antiretroviral agents and abemaciclib, and the potential for increased risk of life-threatening infection with therapy that is myelosuppressive; patients with known hepatitis B or hepatitis C infection are excluded only if there is evidence of active infection (detectable hepatitis B surface antigen, detectable hepatitis C ribonucleic acid [RNA])
• Documented brain metastases that are untreated, symptomatic, or require therapy to control symptoms; participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 7 days prior to trial registration, are neurologically stable, and have recovered from effects of radiotherapy or surgery * Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 2 weeks before the first study drug * Treatment for brain metastases may have included whole brain radiotherapy, radiosurgery, or a combination as was deemed appropriate by the treating physician * Patients who meet the above criteria and are clinically stable on anti-convulsant medication are eligible only if their anti-convulsant does not alter hepatic cytochrome P450 activity in a way that might interfere with metabolism of abemaciclib
• Pregnant women are excluded from this study
• Lactating women are excluding from the study
• Individuals with a history of a second malignancy are ineligible except for the following circumstances: individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if they are diagnosed and have completed treatment within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin; patients with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the principal investigator to determine eligibility
• Have received any live vaccination within 28 days of first dose of study drug
• 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