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project","award":["68611059"],"award-info":[{"award-number":["68611059"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the project","award":["LCF\/TR\/CC20\/52480003"],"award-info":[{"award-number":["LCF\/TR\/CC20\/52480003"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the project","award":["H2020-FETOPEN-2018-2020"],"award-info":[{"award-number":["H2020-FETOPEN-2018-2020"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the project","award":["GA 190138134"],"award-info":[{"award-number":["GA 190138134"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the project","award":["C630926586-00465198"],"award-info":[{"award-number":["C630926586-00465198"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the project","award":["UIDB\/00006\/2020"],"award-info":[{"award-number":["UIDB\/00006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2212 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\u2212 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\u2019s 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] \u2265 6.0 months; 79.1%) and non-responders (PFS &lt; 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 V\u03b42+ 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\u2212 mBC.<\/jats:p>","DOI":"10.3390\/cells13161391","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T03:07:38Z","timestamp":1724296058000},"page":"1391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Cyclin-Dependent Kinase 4\/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5847-7192","authenticated-orcid":false,"given":"Soraia","family":"Lobo-Martins","sequence":"first","affiliation":[{"name":"Academic Trials Promoting Team, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles (U.L.B.), 1070 Bruxelles, Belgium"},{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-3516","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Corredeira","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-1979","authenticated-orcid":false,"given":"Ana","family":"Cavaco","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, 1649-028 Lisbon, Portugal"}]},{"given":"Carolina","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga s\/n, 4715-330 Braga, Portugal"}]},{"given":"Paulina","family":"Piairo","sequence":"additional","affiliation":[{"name":"International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga s\/n, 4715-330 Braga, Portugal"},{"name":"RUBYnanomed Lda, Pra\u00e7a Conde de Agrolongo, 4700-314 Braga, Portugal"}]},{"given":"Cl\u00e1udia","family":"Lopes","sequence":"additional","affiliation":[{"name":"International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga s\/n, 4715-330 Braga, Portugal"}]},{"given":"Joana","family":"Fraga","sequence":"additional","affiliation":[{"name":"RUBYnanomed Lda, Pra\u00e7a Conde de Agrolongo, 4700-314 Braga, Portugal"}]},{"given":"Madalena","family":"Silva","sequence":"additional","affiliation":[{"name":"RUBYnanomed Lda, Pra\u00e7a Conde de Agrolongo, 4700-314 Braga, Portugal"}]},{"given":"Patr\u00edcia","family":"Alves","sequence":"additional","affiliation":[{"name":"START Lisboa-CHULN Hospital Santa Maria, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1438-866X","authenticated-orcid":false,"given":"Lisiana","family":"Wachholz 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Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-0902","authenticated-orcid":false,"given":"Leonor","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"},{"name":"Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, Portugal"}]},{"given":"Catarina","family":"Abreu","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"},{"name":"Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, Portugal"}]},{"given":"Sofia","family":"Torres","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"},{"name":"Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, Portugal"}]},{"given":"Ant\u00f3nio","family":"Quintela","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"}]},{"given":"Gadea","family":"Mata","sequence":"additional","affiliation":[{"name":"Matem\u00e1ticas y Computaci\u00f3n Department, Universidad de La Rioja, 26006 Logro\u00f1o, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-0518","authenticated-orcid":false,"given":"Diego","family":"Meg\u00edas","sequence":"additional","affiliation":[{"name":"Confocal Microscopy Unit, Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO-ISCIII), 28029 Madrid, Spain"}]},{"given":"Julie","family":"Ribot","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, 1649-028 Lisbon, 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Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-6963","authenticated-orcid":false,"given":"Lorena","family":"Di\u00e9guez","sequence":"additional","affiliation":[{"name":"International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga s\/n, 4715-330 Braga, Portugal"},{"name":"RUBYnanomed Lda, Pra\u00e7a Conde de Agrolongo, 4700-314 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7318","authenticated-orcid":false,"given":"Lu\u00eds","family":"Costa","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal"},{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, 1649-028 Lisbon, Portugal"},{"name":"Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.annonc.2021.09.019","article-title":"ESMO Clinical Practice Guideline for the Diagnosis, Staging and Treatment of Patients with Metastatic Breast Cancer","volume":"32","author":"Gennari","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMoa2114663","article-title":"Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer","volume":"386","author":"Hortobagyi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1056\/NEJMoa1903765","article-title":"Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer","volume":"381","author":"Im","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa1911149","article-title":"Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer","volume":"382","author":"Slamon","year":"2020","journal-title":"N. Engl. J. 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