Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Palbociclib

Patients receive SOC treatment consisting of ribociclib or palbociclib plus AI. Patients undergo biopsy of tumor tissue at baseline and post-treatment. Patients also undergo collection of blood samples at baseline, on day 1 of SOC treatment cycles 2, 4, and 6, every 6 cycles thereafter, and at post-treatment.

Patients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis.

Given standard of care ribociclib + AI or palbociclib + AI

Best Practice

Biopsy

Biospecimen Collection

Undergo analysis of previously collected tumor tissue

Laboratory Biomarker Analysis

Yuan Yuan

This clinical trial attempts to understand the differences between two chemotherapy drugs, ribociclib and palbociclib, and how they fight cancer. This study looks at tissue and blood characteristics of patients receiving these therapies in the hopes to develop a way to predict which medication would provide the most benefit to an individual patient.

PRIMARY OBJECTIVE:

I. To identify predictive immune biomarkers and mechanisms of response to ribociclib or palbociclib in advanced, hormone receptor positive breast cancer patients.

SECONDARY OBJECTIVES:

I. Identify changes in antigen presentation machinery and costimulatory molecules on circulating myeloid cells as a result of ribociclib or palbociclib treatment.

II. Characterize the dynamic remodeling of circulating myeloid cell composition that occur as a result of ribociclib or palbociclib treatment.

III. Characterize acquired immune tumor microenvironment features of resistance in patients that progress while undergoing ribociclib or palbociclib treatment.

EXPLORATORY OBJECTIVE:

I. To study the association between immune biomarkers and clinical response.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

PROSPECTIVE COHORT: Patients receive standard of care (SOC) treatment consisting of ribociclib or palbociclib plus aromatase inhibitor (AI). Patients undergo biopsy of tumor tissue at baseline and post-treatment. Patients also undergo collection of blood samples at baseline, on day 1 of SOC treatment cycles 2, 4, and 6, every 6 cycles thereafter, and at post-treatment.

RETROSPECTIVE COHORT: Patients' tumor tissue collected during previous SOC treatment (ribociclib or palbociclib plus AI) is used for analysis.

Effects of Ribociclib and Palbociclib on Tumor and Blood Characteristics in Patients With Metastatic Breast Cancer

Comparative Effects of Ribociclib and Palbociclib on Circulating and Tumor Infiltrating Myeloid Cells in Metastatic Breast Cancer Patients

Will be assessed by high dimensional flow cytometry. One-way analysis of variance (ANOVAs) and non-parametric Kruskal-Wallis tests will be used to compare relative abundances across patient groups and over the course of therapy. Wilcoxon rank-sum test will be used to examine the association between each biomarker of each sample collection and pathological response as appropriate. Odds ratios and 95% conference intervals will be calculated to measure strength of associations. P-values \< 0.05 will be considered statistically significant. No adjustment for multiple comparisons will be used in view of the exploratory nature of this analysis.

Expected to identify \> 30 myeloid and lymphocyte immune subsets. Gene expression relating to maturation and function will be focused on in myeloid subsets especially. Will be assessed by single-cell ribonucleic acid (RNA) sequencing. Immune cell type identification and gene expression patterns will be identified by unsupervised clustering and non-linear dimensionality reduction approaches. Cluster biomarkers will be identified by Seurat for annotating cell types (or functions) for each cell. Within each cluster, will compare the cellular differences in RNA expression across response and non-response cohorts of tumor and peripheral blood mononuclear cell (PBMC) samples by built-in MAST package and Wilcoxon rank-sum test, respectively. Single-cell trajectory analysis for single-cell RNA expression profile will be implemented by Monocle 3 to discover the transitions of cell states in the blood over the course of treatment.

Will be assessed by multiplex immunofluorescence. Cell classifications based on panel design will be created for all cell objects detected in whole slide images of tissues. Tissue segmentation for tumor and stroma areas will be created. Densities of cell classifications within whole tissue, tumor areas, and stroma areas will be calculated. Neighborhood analysis, based off 25micron radius, will be examined using Cytomap to identify patterns of cell-cell interactions within tissues. All quantitative image analysis data between pre-treatment and post-treatment samples will be compared in the context of clinical response to CDK4/6i by Wilcoxon rank-sum tests.

Spots Global Cancer Trial Database for advanced breast adenocarcinoma