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Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

INTRODUCTION: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced...

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Autores principales: Mathiesen, Randi R, Borgen, Elin, Renolen, Anne, Løkkevik, Erik, Nesland, Jahn M, Anker, Gun, Østenstad, Bjørn, Lundgren, Steinar, Risberg, Terje, Mjaaland, Ingvil, Kvalheim, Gunnar, Lønning, Per Eystein, Naume, Bjørn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680942/
https://www.ncbi.nlm.nih.gov/pubmed/22889108
http://dx.doi.org/10.1186/bcr3242
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author Mathiesen, Randi R
Borgen, Elin
Renolen, Anne
Løkkevik, Erik
Nesland, Jahn M
Anker, Gun
Østenstad, Bjørn
Lundgren, Steinar
Risberg, Terje
Mjaaland, Ingvil
Kvalheim, Gunnar
Lønning, Per Eystein
Naume, Bjørn
author_facet Mathiesen, Randi R
Borgen, Elin
Renolen, Anne
Løkkevik, Erik
Nesland, Jahn M
Anker, Gun
Østenstad, Bjørn
Lundgren, Steinar
Risberg, Terje
Mjaaland, Ingvil
Kvalheim, Gunnar
Lønning, Per Eystein
Naume, Bjørn
author_sort Mathiesen, Randi R
collection PubMed
description INTRODUCTION: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. METHODS: Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses. RESULTS: Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months. CONCLUSION: Presence of DTCs after NACT indicated high risk for relapse and death, irrespective of the DTC-status before treatment. The results supports the potential use of DTC analysis as a monitoring tool during follow up, for selection of patients to secondary treatment intervention within clinical trials.
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spelling pubmed-36809422013-06-25 Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival Mathiesen, Randi R Borgen, Elin Renolen, Anne Løkkevik, Erik Nesland, Jahn M Anker, Gun Østenstad, Bjørn Lundgren, Steinar Risberg, Terje Mjaaland, Ingvil Kvalheim, Gunnar Lønning, Per Eystein Naume, Bjørn Breast Cancer Res Research Article INTRODUCTION: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. METHODS: Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses. RESULTS: Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months. CONCLUSION: Presence of DTCs after NACT indicated high risk for relapse and death, irrespective of the DTC-status before treatment. The results supports the potential use of DTC analysis as a monitoring tool during follow up, for selection of patients to secondary treatment intervention within clinical trials. BioMed Central 2012 2012-08-14 /pmc/articles/PMC3680942/ /pubmed/22889108 http://dx.doi.org/10.1186/bcr3242 Text en Copyright ©2012 Mathiesen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mathiesen, Randi R
Borgen, Elin
Renolen, Anne
Løkkevik, Erik
Nesland, Jahn M
Anker, Gun
Østenstad, Bjørn
Lundgren, Steinar
Risberg, Terje
Mjaaland, Ingvil
Kvalheim, Gunnar
Lønning, Per Eystein
Naume, Bjørn
Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title_full Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title_fullStr Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title_full_unstemmed Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title_short Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
title_sort persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680942/
https://www.ncbi.nlm.nih.gov/pubmed/22889108
http://dx.doi.org/10.1186/bcr3242
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