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Breast Cancer Research
Published in: Breast Cancer Research 5/2008

Open Access 01-10-2008 | Research article

A divergent role for estrogen receptor-beta in node-positive and node-negative breast cancer classified according to molecular subtypes: an observational prospective study

Authors: Flavia Novelli, Michele Milella, Elisa Melucci, Anna Di Benedetto, Isabella Sperduti, Raffaele Perrone-Donnorso, Letizia Perracchio, Irene Venturo, Cecilia Nisticò, Alessandra Fabi, Simonetta Buglioni, Pier Giorgio Natali, Marcella Mottolese

Published in: Breast Cancer Research | Issue 5/2008

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Abstract

Introduction

Estrogen receptor-alpha (ER-α) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-β) in various breast cancer risk groups treated with different therapeutic regimens is available. In particular, there are no data concerning ER-β distribution within the novel molecular breast cancer subtypes luminal A (LA) and luminal B (LB), HER2 (HS), and triple-negative (TN).

Methods

We conducted an observational prospective study using immunohistochemistry to evaluate ER-β expression in 936 breast carcinomas. Associations with conventional biopathological factors and with molecular subtypes were analyzed by multiple correspondence analysis (MCA), while univariate and multivariate Cox regression analysis and classification and regression tree analysis were applied to determine the impact of ER-β on disease-free survival in the 728 patients with complete follow-up data.

Results

ER-β evenly distributes (55.5%) across the four molecular breast cancer subtypes, confirming the lack of correlation between ER-β and classical prognosticators. However, the relationships among the biopathological factors, analyzed by MCA, showed that ER-β positivity is located in the quadrant containing more aggressive phenotypes such as HER2 and TN or ER-α/PgR/Bcl2- tumors. Kaplan-Meier curves and Cox regression analysis identified ER-β as a significant discriminating factor for disease-free survival both in the node-negative LA (P = 0.02) subgroup, where it is predictive of response to HT, and in the node-positive LB (P = 0.04) group, where, in association with PgR negativity, it conveys a higher risk of relapse.

Conclusion

Our data indicated that, in contrast to node-negative patients, in node-positive breast cancer patients, ER-β positivity appears to be a biomarker related to a more aggressive clinical course. In this context, further investigations are necessary to better assess the role of the different ER-β isophorms.
Appendix
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Metadata
Title
A divergent role for estrogen receptor-beta in node-positive and node-negative breast cancer classified according to molecular subtypes: an observational prospective study
Authors
Flavia Novelli
Michele Milella
Elisa Melucci
Anna Di Benedetto
Isabella Sperduti
Raffaele Perrone-Donnorso
Letizia Perracchio
Irene Venturo
Cecilia Nisticò
Alessandra Fabi
Simonetta Buglioni
Pier Giorgio Natali
Marcella Mottolese
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2139

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