Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer
The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.
Authors
- Cláudia Lopes (ORCID: https://orcid.org/0000-0003-1792-240X)
- Soraia Lobo-Martins (ORCID: https://orcid.org/0000-0001-5847-7192)
- A Barradas (ORCID: https://orcid.org/0000-0001-6577-6852)
- Karine Serre (ORCID: https://orcid.org/0000-0001-9152-4739)
- Bruno Silva‐Santos (ORCID: https://orcid.org/0000-0003-4141-9302)
- Madalena Pereira da Silva (ORCID: https://orcid.org/0000-0002-8886-2822)
- Julie C. Ribot (ORCID: https://orcid.org/0000-0002-7852-343X)
- Gadea Mata (ORCID: https://orcid.org/0000-0002-5567-8463)
- Lisiana Wachholz Szeneszi (ORCID: https://orcid.org/0009-0002-1438-866X)
- Lorena Diéguez (ORCID: https://orcid.org/0000-0003-3695-6963)
- Sandra Casimiro (ORCID: https://orcid.org/0000-0002-6917-4477)
- Carolina F. Rodrigues (ORCID: https://orcid.org/0000-0002-5493-8331)
- Camila Castro Durán (ORCID: https://orcid.org/0000-0002-2970-420X)
- Patrícia Corredeira (ORCID: https://orcid.org/0000-0001-7075-3516)
- Catarina M. Abreu (ORCID: https://orcid.org/0000-0001-9116-2395)
- Luís Costa (ORCID: https://orcid.org/0000-0002-4782-7318)
- Marília Antunes (ORCID: https://orcid.org/0000-0002-1257-2829)
- Paulina Piairo (ORCID: https://orcid.org/0000-0003-1905-671X)
- Diego Megı́as (ORCID: https://orcid.org/0000-0003-0755-0518)
- Gonçalo Nogueira-Costa (ORCID: https://orcid.org/0000-0002-1127-052X)
- Joana S. Fraga (ORCID: https://orcid.org/0000-0003-3234-0600)
- Conceição Pinto
- Sofía Torres (ORCID: https://orcid.org/0000-0001-6108-6918)
- Ana Cavaco
- Rita Sousa (ORCID: https://orcid.org/0000-0002-9147-7896)
- Leonor Ribeiro (ORCID: https://orcid.org/0000-0002-7657-0902)
- Patrícia Alves (ORCID: https://orcid.org/0000-0002-0650-2445)
- António Quintela
Institutions
- Université Libre de Bruxelles (BE)
- University of Lisbon (PT)
- Universidad de La Rioja (ES)
- Institut Jules Bordet (BE)
- Spanish National Cancer Research Centre (ES)
- International Iberian Nanotechnology Laboratory (PT)
- Hospital de Santa Maria (PT)
- Instituto de Medicina Molecular João Lobo Antunes
Publication Details
- Journal
- Cells
- Published
- 2024-08-21
- DOI
- https://doi.org/10.3390/cells13161391
- Citations
- 2
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 0.84
Funders
- Pfizer
- European Commission