Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer

PRIMARY OBJECTIVE: I. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy regimen without the addition of pembrolizumab (Cohort A). II. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant TNBC patients following a neoadjuvant chemotherapy regimen with the addition of pembrolizumab (Cohort B). SECONDARY OBJECTIVES for Cohort A and Cohort B Independently: I. Assess abemaciclib toxicities. II. To examine the effects of abemaciclib on the percentage of vimentin expressing invasive cancer cells III. Within TNBC molecular subtypes (basal, mesenchymal, and luminal androgen receptor \[LAR\]), to evaluate the effects of abemaciclib on: IIIa. The individual elements of tumor grade (mitoses, nuclear pleomorphism, and tubule formation). IIIb. Tumor proliferation (as measured by tumor Ki-67 and serum tyrosine kinase inhibitor \[TKI\]). IIIc. pDUB3 as well as epithelial-mesenchymal transition (EMT) markers including SNAIL/SLUG, TWIST, and E-Cadherin as measured by immunohistochemistry (IHC). IIId. Quantification of tumor-infiltrating lymphocytes (as examined by hematoxylin and eosin \[H\&E\]). EXPLORATORY OBJECTIVES for Cohort A and Cohort B Independently: I. To evaluate the effect of abemaciclib on tumor ribonucleic acid (RNA) expression. II. To evaluate the effects of abemaciclib on the immune phenotype of peripheral blood mononuclear cells (PBMC), by evaluating expression of a panel of cell surface markers optimized of identification of human immune cell subpopulations. III. To evaluate the effects of abemaciclib on tumor-infiltrating immune cells in formalin-fixed paraffin-embedded (FFPE) tumor sections, using multiplexed imaging technologies (e.g imaging mass cytometry, Nanostring digital spatial profiling \[DSP\] or CODEX) which will include: IIIa. Genes directly involved in tumor cell antigen presentation (e.g. B2M, HLA-A, HLA-B, HLA-C, TAP1, TAP2, TAPBP). IIIb. Interferon-stimulated genes (ISGs) that regulate antigen presentation (e.g. STAT1, NLRC5) and other ISGs (e.g. IRFs, OAS2). IIIc. Genes involved in double-strand ribonucleic acid (dsRNA) response (e.g. DDX58, DHX58). IIId. Genes encoding interferons, including type 3 IFNs (e.g. IFNL1, IFNL2, IFNL3). IIIe. Genes indicating a cytotoxic T cell response (e.g. PRF1, GZMB). IIIf. Regulatory T-cell (Treg)-specific transcription factor genes (e.g. FOXP3, IKZF2). IV. To assess the difference in the frequency of JAK-2 amplification among patients whose post-abemaciclib CD8/FOXP3 ratio \>= 1.6 and that among patients whose post-abemaciclib CD8/FOXP3 ratio \< 1.6. V. To generate organoids for future research. VI. To evaluate changes in the microbiome with exposure to abemaciclib. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive a neoadjuvant chemotherapy regimen without pembrolizumab. GROUP 1: Patients undergo standard of care surgical resection. GROUP 2: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. After completion of study treatment, patients in group 2 are followed up within 30-60 days. COHORT B: Patients receive a neoadjuvant chemotherapy regimen in combination with pembrolizumab. GROUP 3: Patients undergo standard of care surgical resection. GROUP 4: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. After completion of study treatment, patients in group 4 are followed up within 30-60 days.