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Aug 21, 2024;13 (16):

Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

Soraia Lobo-Martins, Patrícia Corredeira, Ana Cavaco, Carolina Rodrigues, Paulina Piairo, Cláudia Lopes, Joana Fraga, Madalena Silva, Patrícia Alves, Lisiana Wachholz Szeneszi, Ana Barradas, Camila Castro Duran, Marília Antunes, Gonçalo Nogueira-Costa, Rita Sousa, Conceição Pinto, Leonor Ribeiro, Catarina Abreu, Sofia Torres, António Quintela, Gadea Mata, Diego Megías, Julie Ribot, Karine Serre, Sandra Casimiro, Bruno Silva-Santos, Lorena Diéguez, Luís Costa
Author Information
  1. Soraia Lobo-Martins: Academic Trials Promoting Team, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), 1070 Bruxelles, Belgium. ORCID
  2. Patrícia Corredeira: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal. ORCID
  3. Ana Cavaco: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal. ORCID
  4. Carolina Rodrigues: International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal.
  5. Paulina Piairo: International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal.
  6. Cláudia Lopes: International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal.
  7. Joana Fraga: RUBYnanomed Lda, Praça Conde de Agrolongo, 4700-314 Braga, Portugal.
  8. Madalena Silva: RUBYnanomed Lda, Praça Conde de Agrolongo, 4700-314 Braga, Portugal.
  9. Patrícia Alves: START Lisboa-CHULN Hospital Santa Maria, 1649-028 Lisbon, Portugal.
  10. Lisiana Wachholz Szeneszi: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
  11. Ana Barradas: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
  12. Camila Castro Duran: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
  13. Marília Antunes: Centro de Estatística e Aplicações, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal.
  14. Gonçalo Nogueira-Costa: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
  15. Rita Sousa: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal.
  16. Conceição Pinto: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal.
  17. Leonor Ribeiro: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
  18. Catarina Abreu: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal.
  19. Sofia Torres: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal.
  20. António Quintela: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal.
  21. Gadea Mata: Matemáticas y Computación Department, Universidad de La Rioja, 26006 Logroño, Spain.
  22. Diego Megías: Confocal Microscopy Unit, Centro Nacional de Investigaciones Oncológicas (CNIO-ISCIII), 28029 Madrid, Spain. ORCID
  23. Julie Ribot: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal.
  24. Karine Serre: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal. ORCID
  25. Sandra Casimiro: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal. ORCID
  26. Bruno Silva-Santos: Instituto de Medicina Molecular João Lobo Antunes, 1649-028 Lisbon, Portugal.
  27. Lorena Diéguez: International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal. ORCID
  28. Luís Costa: Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal. ORCID
PMID: 39195280 DOI: 10.3390/cells13161391

Abstract

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.

Keywords

CDK4/6 inhibitor ER+/HER2− breast cancer advanced breast cancer circulating tumor cell immunomodulation metastatic breast cancer myeloid-derived suppressor cell peripheral immune cell

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Grants

  1. 68611059/Pfizer (Portugal)
  2. CaixaImpulse Grant LCF/TR/CC20/52480003/"La Caixa" Foundation
  3. Call H2020-FETOPEN-2018-2020 in the framework of the BIOCELLPHE project (965018)/European Union
  4. GA 190138134/EIC Accelerator BRIGHT project
  5. C630926586-00465198/Health From Portugal project
  6. Component C5 - Capitalisation and Business Innovation, under the Portuguese Resilience and Recovery Plan, through the NextGenerationEU/NextGenerationEU
  7. UIDB/00006/2020/Fundação para a Ciência e Tecnologia

MeSH Term

Humans
Breast Neoplasms
Female
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Neoplastic Cells, Circulating
Middle Aged
Protein Kinase Inhibitors
Aged
Neoplasm Metastasis
Adult
Prospective Studies

Chemicals

Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Protein Kinase Inhibitors
CDK6 protein, human
Journal Article
Article has an altmetric score of 1

Word Cloud

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