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Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer

BACKGROUND: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive. METHODS: We conducted CTC...

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Autores principales: Vetter, Marcus, Landin, Julia, Szczerba, Barbara Maria, Castro-Giner, Francesc, Gkountela, Sofia, Donato, Cinzia, Krol, Ilona, Scherrer, Ramona, Balmelli, Catharina, Malinovska, Alexandra, Zippelius, Alfred, Kurzeder, Christian, Heinzelmann-Schwarz, Viola, Weber, Walter Paul, Rochlitz, Christoph, Aceto, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247738/
https://www.ncbi.nlm.nih.gov/pubmed/30458879
http://dx.doi.org/10.1186/s13058-018-1067-y
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author Vetter, Marcus
Landin, Julia
Szczerba, Barbara Maria
Castro-Giner, Francesc
Gkountela, Sofia
Donato, Cinzia
Krol, Ilona
Scherrer, Ramona
Balmelli, Catharina
Malinovska, Alexandra
Zippelius, Alfred
Kurzeder, Christian
Heinzelmann-Schwarz, Viola
Weber, Walter Paul
Rochlitz, Christoph
Aceto, Nicola
author_facet Vetter, Marcus
Landin, Julia
Szczerba, Barbara Maria
Castro-Giner, Francesc
Gkountela, Sofia
Donato, Cinzia
Krol, Ilona
Scherrer, Ramona
Balmelli, Catharina
Malinovska, Alexandra
Zippelius, Alfred
Kurzeder, Christian
Heinzelmann-Schwarz, Viola
Weber, Walter Paul
Rochlitz, Christoph
Aceto, Nicola
author_sort Vetter, Marcus
collection PubMed
description BACKGROUND: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive. METHODS: We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized by progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation. CTCs were quantified with the Parsortix microfluidic device. Clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling were evaluated for each patient. RESULTS: Among 73 patients, we detected at least one CTC per 7.5 ml of blood in 34 (46%). Of these, 22 (65%) had single CTCs only, whereas 12 (35%) featured both single CTCs and CTC clusters. Treatment with the monoclonal antibody denosumab correlated with the absence of CTCs, both when considering all patients and when considering only those with bone metastasis. We also found that low red blood cell count was associated with the presence of CTCs, whereas high CA 15-3 tumor marker, high mean corpuscular volume, high white blood cell count and high mean platelet volume associated specifically with CTC clusters. CONCLUSIONS: In addition to blood count correlatives to single and clustered CTCs, we found that denosumab treatment associates with most patients lacking CTCs from their peripheral circulation. Prospective studies will be needed to validate the involvement of denosumab in the prevention of CTC generation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-1067-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-62477382018-11-26 Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer Vetter, Marcus Landin, Julia Szczerba, Barbara Maria Castro-Giner, Francesc Gkountela, Sofia Donato, Cinzia Krol, Ilona Scherrer, Ramona Balmelli, Catharina Malinovska, Alexandra Zippelius, Alfred Kurzeder, Christian Heinzelmann-Schwarz, Viola Weber, Walter Paul Rochlitz, Christoph Aceto, Nicola Breast Cancer Res Research Article BACKGROUND: The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive. METHODS: We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized by progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation. CTCs were quantified with the Parsortix microfluidic device. Clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling were evaluated for each patient. RESULTS: Among 73 patients, we detected at least one CTC per 7.5 ml of blood in 34 (46%). Of these, 22 (65%) had single CTCs only, whereas 12 (35%) featured both single CTCs and CTC clusters. Treatment with the monoclonal antibody denosumab correlated with the absence of CTCs, both when considering all patients and when considering only those with bone metastasis. We also found that low red blood cell count was associated with the presence of CTCs, whereas high CA 15-3 tumor marker, high mean corpuscular volume, high white blood cell count and high mean platelet volume associated specifically with CTC clusters. CONCLUSIONS: In addition to blood count correlatives to single and clustered CTCs, we found that denosumab treatment associates with most patients lacking CTCs from their peripheral circulation. Prospective studies will be needed to validate the involvement of denosumab in the prevention of CTC generation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-1067-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-20 2018 /pmc/articles/PMC6247738/ /pubmed/30458879 http://dx.doi.org/10.1186/s13058-018-1067-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Vetter, Marcus
Landin, Julia
Szczerba, Barbara Maria
Castro-Giner, Francesc
Gkountela, Sofia
Donato, Cinzia
Krol, Ilona
Scherrer, Ramona
Balmelli, Catharina
Malinovska, Alexandra
Zippelius, Alfred
Kurzeder, Christian
Heinzelmann-Schwarz, Viola
Weber, Walter Paul
Rochlitz, Christoph
Aceto, Nicola
Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title_full Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title_fullStr Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title_full_unstemmed Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title_short Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
title_sort denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247738/
https://www.ncbi.nlm.nih.gov/pubmed/30458879
http://dx.doi.org/10.1186/s13058-018-1067-y
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