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The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer
BACKGROUND: A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831058/ https://www.ncbi.nlm.nih.gov/pubmed/20209131 http://dx.doi.org/10.1371/journal.pone.0009499 |
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author | Margeli, Mireia Cirauqui, Beatriz Castella, Eva Tapia, Gustavo Costa, Carlota Gimenez-Capitan, Ana Barnadas, Agusti Ronco, Maria Sanchez Benlloch, Susana Taron, Miquel Rosell, Rafael |
author_facet | Margeli, Mireia Cirauqui, Beatriz Castella, Eva Tapia, Gustavo Costa, Carlota Gimenez-Capitan, Ana Barnadas, Agusti Ronco, Maria Sanchez Benlloch, Susana Taron, Miquel Rosell, Rafael |
author_sort | Margeli, Mireia |
collection | PubMed |
description | BACKGROUND: A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1 mRNA have longer survival following platinum-based chemotherapy than patients with high levels of BRCA1 mRNA. METHODOLOGY/PRINCIPAL FINDINGS: Tumor biopsies were obtained from 86 breast cancer patients who were candidates for neoadjuvant chemotherapy, treated with four cycles of neoadjuvant fluorouracil, epirubicin and cyclophosphamide. Estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 and vimentin were examined by tissue microarray. HER2 were also assessed by chromogenic in situ hybridization, and BRCA1 mRNA was analyzed in a subset of 41 patients for whom sufficient tumor tissue was available by real-time quantitative PCR. Median time to progression was 42 months and overall survival was 55 months. In the multivariate analysis for time to progression and overall survival for 41 patients in whom BRCA1 could be assessed, low levels of BRCA1 mRNA, positive PR and negative lymph node involvement predicted a significantly lower risk of relapse, low levels of BRCA1 mRNA and positive PR were the only variables associated with significantly longer survival. CONCLUSIONS/SIGNIFICANCE: We provide evidence for a major role for BRCA1 mRNA expression as a marker of time to progression and overall survival in sporadic breast cancers treated with anthracycline-based chemotherapy. These findings can be useful for customizing chemotherapy. |
format | Text |
id | pubmed-2831058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28310582010-03-06 The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer Margeli, Mireia Cirauqui, Beatriz Castella, Eva Tapia, Gustavo Costa, Carlota Gimenez-Capitan, Ana Barnadas, Agusti Ronco, Maria Sanchez Benlloch, Susana Taron, Miquel Rosell, Rafael PLoS One Research Article BACKGROUND: A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1 mRNA have longer survival following platinum-based chemotherapy than patients with high levels of BRCA1 mRNA. METHODOLOGY/PRINCIPAL FINDINGS: Tumor biopsies were obtained from 86 breast cancer patients who were candidates for neoadjuvant chemotherapy, treated with four cycles of neoadjuvant fluorouracil, epirubicin and cyclophosphamide. Estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 and vimentin were examined by tissue microarray. HER2 were also assessed by chromogenic in situ hybridization, and BRCA1 mRNA was analyzed in a subset of 41 patients for whom sufficient tumor tissue was available by real-time quantitative PCR. Median time to progression was 42 months and overall survival was 55 months. In the multivariate analysis for time to progression and overall survival for 41 patients in whom BRCA1 could be assessed, low levels of BRCA1 mRNA, positive PR and negative lymph node involvement predicted a significantly lower risk of relapse, low levels of BRCA1 mRNA and positive PR were the only variables associated with significantly longer survival. CONCLUSIONS/SIGNIFICANCE: We provide evidence for a major role for BRCA1 mRNA expression as a marker of time to progression and overall survival in sporadic breast cancers treated with anthracycline-based chemotherapy. These findings can be useful for customizing chemotherapy. Public Library of Science 2010-03-03 /pmc/articles/PMC2831058/ /pubmed/20209131 http://dx.doi.org/10.1371/journal.pone.0009499 Text en Margeli et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Margeli, Mireia Cirauqui, Beatriz Castella, Eva Tapia, Gustavo Costa, Carlota Gimenez-Capitan, Ana Barnadas, Agusti Ronco, Maria Sanchez Benlloch, Susana Taron, Miquel Rosell, Rafael The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title | The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title_full | The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title_fullStr | The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title_full_unstemmed | The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title_short | The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer |
title_sort | prognostic value of brca1 mrna expression levels following neoadjuvant chemotherapy in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831058/ https://www.ncbi.nlm.nih.gov/pubmed/20209131 http://dx.doi.org/10.1371/journal.pone.0009499 |
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