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Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1
BACKGROUND: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. T...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587293/ https://www.ncbi.nlm.nih.gov/pubmed/28877230 http://dx.doi.org/10.1371/journal.pone.0183917 |
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author | Ettl, Johannes Klein, Evelyn Hapfelmeier, Alexander Grosse Lackmann, Kirsten Paepke, Stefan Petry, Christoph Specht, Katja Wolff, Laura Höfler, Heinz Kiechle, Marion |
author_facet | Ettl, Johannes Klein, Evelyn Hapfelmeier, Alexander Grosse Lackmann, Kirsten Paepke, Stefan Petry, Christoph Specht, Katja Wolff, Laura Höfler, Heinz Kiechle, Marion |
author_sort | Ettl, Johannes |
collection | PubMed |
description | BACKGROUND: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation. MATERIALS AND METHOD: 395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman’s rank correlation coefficient and Cohen’s Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1. RESULTS: EPclin could be determined in all 395 (100%), uPA/PAI-1 in 190 (48%) of the tumor samples. EPclin allocated 250 patients (63%) to the low-risk group and 145 patients (37%) to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46%) to the low-risk group and 102 patients (54%) to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%). Recommendation of adjuvant chemotherapy (CTX) was abandoned twice as often by EPclin (45%) compared to uPA/PAI-1 (22%). CONCLUSION: In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing. |
format | Online Article Text |
id | pubmed-5587293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55872932017-09-15 Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 Ettl, Johannes Klein, Evelyn Hapfelmeier, Alexander Grosse Lackmann, Kirsten Paepke, Stefan Petry, Christoph Specht, Katja Wolff, Laura Höfler, Heinz Kiechle, Marion PLoS One Research Article BACKGROUND: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation. MATERIALS AND METHOD: 395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman’s rank correlation coefficient and Cohen’s Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1. RESULTS: EPclin could be determined in all 395 (100%), uPA/PAI-1 in 190 (48%) of the tumor samples. EPclin allocated 250 patients (63%) to the low-risk group and 145 patients (37%) to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46%) to the low-risk group and 102 patients (54%) to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%). Recommendation of adjuvant chemotherapy (CTX) was abandoned twice as often by EPclin (45%) compared to uPA/PAI-1 (22%). CONCLUSION: In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing. Public Library of Science 2017-09-06 /pmc/articles/PMC5587293/ /pubmed/28877230 http://dx.doi.org/10.1371/journal.pone.0183917 Text en © 2017 Ettl 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ettl, Johannes Klein, Evelyn Hapfelmeier, Alexander Grosse Lackmann, Kirsten Paepke, Stefan Petry, Christoph Specht, Katja Wolff, Laura Höfler, Heinz Kiechle, Marion Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title | Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title_full | Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title_fullStr | Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title_full_unstemmed | Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title_short | Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1 |
title_sort | decision impact and feasibility of different asco-recommended biomarkers in early breast cancer: prospective comparison of molecular marker endopredict and protein marker upa/pai-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587293/ https://www.ncbi.nlm.nih.gov/pubmed/28877230 http://dx.doi.org/10.1371/journal.pone.0183917 |
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