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Updated: Jun 16, 2025
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Baseline cell cycle and immune profiles indicate CDK4/6 inhibitor response in metastatic HR + /HER2- breast cancer
Stephanie L Tzetzo1, Emily Schultz1, Jianxin Wang1
1Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Abstract:
While CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are standard-of-care for metastatic HR + /HER2- breast cancer, patient selection for durable efficacy remains undefined. Here, we assessed baseline cell cycle and immune profiles in a CDK4/6i-treated patient cohort with differential progression-free survival (PFS < 6 months vs. >23 months) using transcriptomic and protein-based imaging approaches. Cell cycle, polo-like kinase signaling and transcription gene sets are largely enriched among pre-treatment tissue of patients with short PFS. Pre-treatment tumors express cyclin A or E significantly higher in patients with short PFS and correlate with macrophage accumulation. Patients with long PFS display gene set enrichment for growth factor and immune signaling pre-treatment, while gene set enrichment for immune activation emerges during CDK4/6i therapy. Our data highlight baseline tumor-intrinsic and tumor microenvironments-associated indicators of CDK4/6i response in the "real-world" setting and offer implications for precision-based therapeutic combinations to enhance CDK4/6i efficacy. Clinical trial registration number: NCT04526587.
Insights
Identifying biomarkers for CDK4/6 inhibitors (CDK4/6i) in metastatic HR+/HER2- breast cancer is crucial. Baseline cell cycle and immune profiles predict patient response to CDK4/6i therapy, guiding personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Standard-of-care for metastatic HR+/HER2- breast cancer involves CDK4/6 inhibitors (CDK4/6i) and endocrine therapy.
- Predicting durable efficacy and selecting patients for CDK4/6i treatment remains a challenge.
Purpose of the Study:
- To identify baseline cell cycle and immune profiles associated with differential progression-free survival (PFS) in patients treated with CDK4/6i.
- To explore transcriptomic and protein-based imaging markers for predicting CDK4/6i response.
Main Methods:
- Analysis of baseline transcriptomic and protein-based imaging data from a cohort of CDK4/6i-treated metastatic HR+/HER2- breast cancer patients.
- Comparison of molecular profiles between patients with short PFS (<6 months) and long PFS (>23 months).
Main Results:
- Enrichment of cell cycle, polo-like kinase signaling, and transcription gene sets in pre-treatment tumors of patients with short PFS.
- Higher pre-treatment expression of cyclin A or E in short PFS patients, correlating with macrophage accumulation.
- Pre-treatment enrichment of growth factor and immune signaling in long PFS patients, with immune activation emerging during therapy.
Conclusions:
- Baseline tumor-intrinsic and microenvironment factors indicate CDK4/6i response in real-world settings.
- Identified indicators can inform precision-based combinations to improve CDK4/6i efficacy.
- Clinical trial NCT04526587 provides a basis for further investigation.
