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Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer
BACKGROUND: The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER–) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER−/PgR+/HER2− phenotype. METHODS...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595063/ https://www.ncbi.nlm.nih.gov/pubmed/26437901 http://dx.doi.org/10.1186/s12916-015-0496-z |
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author | Yu, Ke-Da Jiang, Yi-Zhou Hao, Shuang Shao, Zhi-Ming |
author_facet | Yu, Ke-Da Jiang, Yi-Zhou Hao, Shuang Shao, Zhi-Ming |
author_sort | Yu, Ke-Da |
collection | PubMed |
description | BACKGROUND: The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER–) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER−/PgR+/HER2− phenotype. METHODS: Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER–/PgR+/HER2– phenotype were determined and further validated. RESULTS: Clinicopathologic features and survival outcomes of the ER–/PgR+ phenotype fell in between the ER+/PgR+ and ER−/PgR− phenotypes, but were more similar to ER−/PgR−. Among the ER−/PgR+ phenotype, 30 % (95 % confidence interval [CI] 17–42 %, pooled by a fixed-effects method) were luminal-like and 59 % (95 % CI 45–72 %, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER−/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER−/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER−/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER−/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER−/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). CONCLUSIONS: The majority of ER−/PgR+/HER2– phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0496-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4595063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45950632015-10-07 Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer Yu, Ke-Da Jiang, Yi-Zhou Hao, Shuang Shao, Zhi-Ming BMC Med Research Article BACKGROUND: The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER–) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER−/PgR+/HER2− phenotype. METHODS: Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER–/PgR+/HER2– phenotype were determined and further validated. RESULTS: Clinicopathologic features and survival outcomes of the ER–/PgR+ phenotype fell in between the ER+/PgR+ and ER−/PgR− phenotypes, but were more similar to ER−/PgR−. Among the ER−/PgR+ phenotype, 30 % (95 % confidence interval [CI] 17–42 %, pooled by a fixed-effects method) were luminal-like and 59 % (95 % CI 45–72 %, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER−/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER−/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER−/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER−/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER−/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). CONCLUSIONS: The majority of ER−/PgR+/HER2– phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0496-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-05 /pmc/articles/PMC4595063/ /pubmed/26437901 http://dx.doi.org/10.1186/s12916-015-0496-z Text en © Yu et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Yu, Ke-Da Jiang, Yi-Zhou Hao, Shuang Shao, Zhi-Ming Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title | Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title_full | Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title_fullStr | Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title_full_unstemmed | Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title_short | Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer |
title_sort | molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and her2-negative breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595063/ https://www.ncbi.nlm.nih.gov/pubmed/26437901 http://dx.doi.org/10.1186/s12916-015-0496-z |
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