Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers.

Maria M Litwiniuk,Małgorzata Stawicka,Krzysztof Rożnowski,Violetta Filas,Jan Bręborowicz,Dariusz D Godlewski,Remigiusz Kaleta

doi:10.1186/1471-2407-8-100

Maria M Litwiniuk, Małgorzata Stawicka + Show 5 more

Open Access

https://doi.org/10.1186/1471-2407-8-100

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Journal: BMC Cancer	Publication Date: Apr 13, 2008
Citations: 62	License type: cc-by

Affiliation: Poznan University of Medical Sciences

Abstract

BackgroundBreast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERα, ERβ, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated BRCA1 gene and in the control group.MethodsThe study group consisted of 48 women with BRCA1 gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and polyclonal antibody against ERβ (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998–99.ResultsThe results of our investigation showed that BRCA1 mutation carriers were more likely to have ERα-negative breast cancer than those in the control group. Only 14.5% of BRCA1-related cancers were ERα-positive compared with 57.5% in the control group (P < 0.0001). On the contrary, the expression of ERβ protein was observed in 42% of BRCA1-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERα(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERβ.ConclusionIn the case of BRCA1-associated tumors the expression of ERβ was significantly higher than the expression of ERα. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in BRCA1 mutation carriers.

Highlights

Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC
Other tumor types were much less frequent, it is noteworthy that all 5 patients with "medullary like" carcinoma came from the BRCA1 mutation carriers group (10%)
The results obtained in our study show that the expression of Estrogen receptor β (ERβ) in BRCA1 gene mutation carriers is statistically higher than the expression of ERα

Summary

Introduction

Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Breast cancer associated with this mutation has characteristic histopathological features: (i) the expression of estrogen and progesterone receptors is less frequently demonstrable, (ii) the grade of histopathological malignancy is higher and (iii) accumulation of p53 protein is observed more often than in sporadic cases of this malignancy [8,9]. These factors are usually associated with a poorer prognosis, their role in BRCA1 and BRCA2 mutation carriers is still controversial [10,11,12,13,14,15]

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