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An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer

BACKGROUND: The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their pro...

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Autores principales: Lee, H E, Kim, J H, Kim, Y J, Choi, S Y, Kim, S-W, Kang, E, Chung, I Y, Kim, I A, Kim, E J, Choi, Y, Ryu, H S, Park, S Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111169/
https://www.ncbi.nlm.nih.gov/pubmed/21559013
http://dx.doi.org/10.1038/bjc.2011.159
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author Lee, H E
Kim, J H
Kim, Y J
Choi, S Y
Kim, S-W
Kang, E
Chung, I Y
Kim, I A
Kim, E J
Choi, Y
Ryu, H S
Park, S Y
author_facet Lee, H E
Kim, J H
Kim, Y J
Choi, S Y
Kim, S-W
Kang, E
Chung, I Y
Kim, I A
Kim, E J
Choi, Y
Ryu, H S
Park, S Y
author_sort Lee, H E
collection PubMed
description BACKGROUND: The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer. METHODS: Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24− or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry. RESULTS: A higher proportion of CD44+/CD24− tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24− and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24− tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen. CONCLUSION: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.
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spelling pubmed-31111692012-05-24 An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer Lee, H E Kim, J H Kim, Y J Choi, S Y Kim, S-W Kang, E Chung, I Y Kim, I A Kim, E J Choi, Y Ryu, H S Park, S Y Br J Cancer Translational Therapeutics BACKGROUND: The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer. METHODS: Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24− or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry. RESULTS: A higher proportion of CD44+/CD24− tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24− and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24− tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen. CONCLUSION: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics. Nature Publishing Group 2011-05-24 2011-05-10 /pmc/articles/PMC3111169/ /pubmed/21559013 http://dx.doi.org/10.1038/bjc.2011.159 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Lee, H E
Kim, J H
Kim, Y J
Choi, S Y
Kim, S-W
Kang, E
Chung, I Y
Kim, I A
Kim, E J
Choi, Y
Ryu, H S
Park, S Y
An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title_full An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title_fullStr An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title_full_unstemmed An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title_short An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
title_sort increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111169/
https://www.ncbi.nlm.nih.gov/pubmed/21559013
http://dx.doi.org/10.1038/bjc.2011.159
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