Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes

INTRODUCTION: Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer...

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Autors principals: Habibi, Golareh, Leung, Samuel, Law, Jennifer H, Gelmon, Karen, Masoudi, Hamid, Turbin, Dmitry, Pollak, Michael, Nielsen, Torsten O, Huntsman, David, Dunn, Sandra E
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Publicat: BioMed Central 2008
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Accés en línia:https://ncbi.nlm.nih.gov/pmc/articles/PMC2614522/
https://ncbi.nlm.nih.gov/pubmed/18925950
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1186/bcr2156
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spelling pubmed-26145222009-01-08 Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes Habibi, Golareh Leung, Samuel Law, Jennifer H Gelmon, Karen Masoudi, Hamid Turbin, Dmitry Pollak, Michael Nielsen, Torsten O Huntsman, David Dunn, Sandra E Breast Cancer Res Research Article INTRODUCTION: Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previously reported that Y-box binding protein-1 (YB-1), a transcription/translation factor, was a marker of poor prognosis in a cohort of 490 patients with breast cancer, but the study was not large enough to subtype the cancers. We therefore investigated whether YB-1 identifies patients at risk for either reduced relapse free survival or decreased r breast cancer specific survival (BCSS) across all tumor subtypes by evaluating 4,049 cases. METHODS: Tumor tissue microarrays, representing 4,049 cases of invasive breast cancers with 20 years of follow up, were subtyped by the expression profiles of estrogen receptor, progesterone receptor, or HER-2. We then addressed whether YB-1 expression identified patients at higher risk for relapse and/or lower BCSS. RESULTS: We found YB-1 to be a highly predictive biomarker of relapse (P < 2.5 × 10(-20)) and poor survival (P < 7.3 × 10(-26)) in the entire cohort and across all breast cancer subtypes. Patients with node-positive or node-negative cancer were more likely to die from the disease if YB-1 was expressed. This was further substantiated using a Cox regression model, which revealed that it was significantly associated with relapse and poor survival in a subtype independent manner (relapse patients, hazard ratio = 1.28, P < 8 × 10(-3); all patients, hazard ratio = 1.45, P < 6.7 × 10(-7)). Moreover, YB-1 was superior to estrogen receptor and HER-2 as a prognostic marker for relapse and survival. For a subset of patients who were originally considered low risk and were therefore not given chemotherapy, YB-1 was indicative of poor survival (P < 7.1 × 10 (-17)). Likewise, YB-1 was predictive of decreased BCSS in tamoxifen-treated patients (P = 0.001); in this setting a Cox regression model once again demonstrated it to be an independent biomarker indicating poor survival (hazard ratio = 1.70, P = 0.022). CONCLUSIONS: Expression of YB-1 universally identifies patients at high risk across all breast cancer subtypes and in situations where more aggressive treatment may be needed. We therefore propose that YB-1 may re-define high-risk breast cancer and thereby create opportunities for individualized therapy. BioMed Central 2008 2008-10-16 /pmc/articles/PMC2614522/ /pubmed/18925950 http://dx.doi.org/10.1186/bcr2156 Text en Copyright © 2008 Habibi 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.
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Research Article
spellingShingle Research Article
Habibi, Golareh
Leung, Samuel
Law, Jennifer H
Gelmon, Karen
Masoudi, Hamid
Turbin, Dmitry
Pollak, Michael
Nielsen, Torsten O
Huntsman, David
Dunn, Sandra E
Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
description INTRODUCTION: Gene expression analysis is used to subtype breast cancers such that the most aggressive tumors are identified, but translating this into clinical practice can be cumbersome. Our goal is to develop a universal biomarker that distinguishes patients at high risk across all breast cancer subtypes. We previously reported that Y-box binding protein-1 (YB-1), a transcription/translation factor, was a marker of poor prognosis in a cohort of 490 patients with breast cancer, but the study was not large enough to subtype the cancers. We therefore investigated whether YB-1 identifies patients at risk for either reduced relapse free survival or decreased r breast cancer specific survival (BCSS) across all tumor subtypes by evaluating 4,049 cases. METHODS: Tumor tissue microarrays, representing 4,049 cases of invasive breast cancers with 20 years of follow up, were subtyped by the expression profiles of estrogen receptor, progesterone receptor, or HER-2. We then addressed whether YB-1 expression identified patients at higher risk for relapse and/or lower BCSS. RESULTS: We found YB-1 to be a highly predictive biomarker of relapse (P < 2.5 × 10(-20)) and poor survival (P < 7.3 × 10(-26)) in the entire cohort and across all breast cancer subtypes. Patients with node-positive or node-negative cancer were more likely to die from the disease if YB-1 was expressed. This was further substantiated using a Cox regression model, which revealed that it was significantly associated with relapse and poor survival in a subtype independent manner (relapse patients, hazard ratio = 1.28, P < 8 × 10(-3); all patients, hazard ratio = 1.45, P < 6.7 × 10(-7)). Moreover, YB-1 was superior to estrogen receptor and HER-2 as a prognostic marker for relapse and survival. For a subset of patients who were originally considered low risk and were therefore not given chemotherapy, YB-1 was indicative of poor survival (P < 7.1 × 10 (-17)). Likewise, YB-1 was predictive of decreased BCSS in tamoxifen-treated patients (P = 0.001); in this setting a Cox regression model once again demonstrated it to be an independent biomarker indicating poor survival (hazard ratio = 1.70, P = 0.022). CONCLUSIONS: Expression of YB-1 universally identifies patients at high risk across all breast cancer subtypes and in situations where more aggressive treatment may be needed. We therefore propose that YB-1 may re-define high-risk breast cancer and thereby create opportunities for individualized therapy.
author Habibi, Golareh
Leung, Samuel
Law, Jennifer H
Gelmon, Karen
Masoudi, Hamid
Turbin, Dmitry
Pollak, Michael
Nielsen, Torsten O
Huntsman, David
Dunn, Sandra E
author_facet Habibi, Golareh
Leung, Samuel
Law, Jennifer H
Gelmon, Karen
Masoudi, Hamid
Turbin, Dmitry
Pollak, Michael
Nielsen, Torsten O
Huntsman, David
Dunn, Sandra E
author_sort Habibi, Golareh
title Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
title_short Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
title_full Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
title_fullStr Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
title_full_unstemmed Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes
title_sort redefining prognostic factors for breast cancer: yb-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or her-2 across all tumor subtypes
publisher BioMed Central
publisher_facet BioMed Central
publishDate 2008
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2614522/
https://ncbi.nlm.nih.gov/pubmed/18925950
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1186/bcr2156
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