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Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers
Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate mole...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919784/ https://www.ncbi.nlm.nih.gov/pubmed/24520381 http://dx.doi.org/10.1371/journal.pone.0088401 |
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author | Schleifman, Erica B. Desai, Rupal Spoerke, Jill M. Xiao, Yuanyuan Wong, Cheryl Abbas, Ilma O’Brien, Carol Patel, Rajesh Sumiyoshi, Teiko Fu, Ling Tam, Rachel N. Koeppen, Hartmut Wilson, Timothy R. Raja, Rajiv Hampton, Garret M. Lackner, Mark R. |
author_facet | Schleifman, Erica B. Desai, Rupal Spoerke, Jill M. Xiao, Yuanyuan Wong, Cheryl Abbas, Ilma O’Brien, Carol Patel, Rajesh Sumiyoshi, Teiko Fu, Ling Tam, Rachel N. Koeppen, Hartmut Wilson, Timothy R. Raja, Rajiv Hampton, Garret M. Lackner, Mark R. |
author_sort | Schleifman, Erica B. |
collection | PubMed |
description | Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K) pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE) tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies. |
format | Online Article Text |
id | pubmed-3919784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39197842014-02-11 Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers Schleifman, Erica B. Desai, Rupal Spoerke, Jill M. Xiao, Yuanyuan Wong, Cheryl Abbas, Ilma O’Brien, Carol Patel, Rajesh Sumiyoshi, Teiko Fu, Ling Tam, Rachel N. Koeppen, Hartmut Wilson, Timothy R. Raja, Rajiv Hampton, Garret M. Lackner, Mark R. PLoS One Research Article Patients with newly diagnosed, early stage estrogen receptor positive (ER+) breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K) pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE) tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies. Public Library of Science 2014-02-10 /pmc/articles/PMC3919784/ /pubmed/24520381 http://dx.doi.org/10.1371/journal.pone.0088401 Text en © 2014 Schleifman 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 Schleifman, Erica B. Desai, Rupal Spoerke, Jill M. Xiao, Yuanyuan Wong, Cheryl Abbas, Ilma O’Brien, Carol Patel, Rajesh Sumiyoshi, Teiko Fu, Ling Tam, Rachel N. Koeppen, Hartmut Wilson, Timothy R. Raja, Rajiv Hampton, Garret M. Lackner, Mark R. Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title | Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title_full | Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title_fullStr | Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title_full_unstemmed | Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title_short | Targeted Biomarker Profiling of Matched Primary and Metastatic Estrogen Receptor Positive Breast Cancers |
title_sort | targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919784/ https://www.ncbi.nlm.nih.gov/pubmed/24520381 http://dx.doi.org/10.1371/journal.pone.0088401 |
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