J Breast Cancer JBC Journal of Breast Cancer 1738-6756 Korean Breast Cancer Society 10.4048/jbc.2009.12.3.156 Original Article The Clinical Significance of the Estrogen Receptor β Expression for Endocrine Therapy in Patients with ERα-negative and Progesterone Receptor-positive Breast Carcinoma Park Min Ho Ryu Hee Seon Ro Hye Won Cho Jin Seong Yoon Jung Han Jegal Young Jong Kim Jo Heon 1 Lee Ji Shin 1 Park Chang Soo 1 Department of Surgery, Chonnam National University Hwasun Hospital, Gwangju, Korea. Department of Pathology, Chonnam National University Hwasun Hospital, Gwangju, Korea. Corresponding author (thokthok@hanmail.net) 09 2009 28 09 2009 12 3 156 162 12 02 2009 11 06 2009 Copyright © 2009 Korean Breast Cancer Society 2009 Purpose

Estrogen receptor (ER) is the key therapeutic target in breast cancer. ERβ has recently been identified to be distinct from ERα. In contrast to ERα, the functions of ERβ in breast cancer are still unclear. We sought to determine whether the expression of ERβ can be used as a predictive marker for endocrine therapy for patients with ERα-negative breast cancer.

 Methods

Formalin-fixed, paraffin-embedded tumor specimens from 52 patients with ER-/PR+ invasive breast cancer were immunostained for their ERβ expression. These patients were treated with adjuvant tamoxifen. The results were correlated with various clinicopathological variables and the follow-up data. The expressions of p53 and HER-2/neu were also analyzed and correlated with the ERβ status.

 Results

An ERβ expression was observed in 53.8% (28/52) of the breast cancer samples. There was no correlation between the ERβ expression and the other clinicopathologic factors (age, tumor size, histologic type, nodal status, histological grade, stage, therapeutic modality, progesterone receptor (PR) expression, p53 expression and HER-2/neu expression). Recurrence was present in 7.7% (2/26) of the patients whose tumors had an ERβ expression, as compared to the presence of recurrence in 36.4% (8/22) of the patients whose tumors had no ERβ expression (p<0.05). The patients with ERβ negative-tumors revealed lower disease free survival rate than those with ERβ positive-tumors (p<0.05). Of the 52 patients, 10 (19.2%) were p53 positive, and 11 (21.2%) were HER-2/neu positive. No significant correlations were observed between ERβ and p53 or HER-2/neu.

 Conclusion

These results suggest that ERβ might be a predictive marker of a response to endocrine therapy in patients with ER-/PR+ invasive breast cancer, although this needs to be confirmed by additional studies.

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Immunoreactivity for ERβ. (A) In normal breast lobules, the protein expressed in the majority of luminal epithelial cells (×400).

(B) Intense immunoreactivity for ERβ is noted in the nuclei of an invasive ductal carcinoma (×200).

ERβ=estrogen receptor beta.

Kaplan-Meier curves for ERβ expression in breast carcinoma patients. Patients with ERβ negative-tumors suffered a significantly decreased disease free survival (log-rank test, p<0.05).

ERβ=estrogen receptor beta.

Invasive ductal carcinoma with intense nuclear staining for p53 (×200).

Invasive ductal carcinoma with intense membrane staining for HER-2/neu (×200).

Characteristics of the patient population

BCS=breast conservation surgery.

Relationship between ERβ expression and clinicopathologic factors

ERβ=estrogen receptor beta; BCS=breast conservation surgery; PR=progesterone receptor.

*p-values obtained using χ2 test.

Univariate analysis of DFS and OS by prognostic factors for patients with breast carcinoma

DFS=disease free survival; OS=overall survival; BCS=breast conservation surgery; ERα=estrogen receptor beta; PR=progesterone receptor.