Significance of ERβ expression in different molecular subtypes of breast cancer

Guo, Li; Meng, Jie; Yilamu, Dilimina; Jakulin, Adina; Fu, Minggang; Wang, Bowei; Abulajiang, Gulinaer

doi:10.1186/1746-1596-9-20

Cited by 15 publications

(11 citation statements)

References 21 publications

(19 reference statements)

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“…ERβ positivity (96.8%) in our series is much higher than that in previous studies, which reported rates of 25% in triple-negative cancers54 and 37.6% in basal-like breast cancers 55. To the best of our knowledge, there have been no reports of ERβ on purely metastatic TNBC.…”

Section: Discussioncontrasting

confidence: 74%

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

Goto¹,

Thike

Ong

et al. 2019

J Clin Pathol

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AimsCharacterising the factors responsible for metastatic triple-negative breast cancer (TNBC) is of significant importance, considering its high mortality rate and scant data. In this study, we evaluated the characteristics, clinical behaviour and role of biomarkers (androgen receptor (AR), oestrogen receptor beta (ERβ) and p53) in metastatic TNBC.MethodsImmunohistochemistry was performed for AR, ERβ and p53 on 125 primary TNBCs with known metastasis and correlated with clinicopathological parameters and outcome. AR and p53 mRNA profiling was also carried out on 34 tumours from the same series and correlated with outcomes.ResultsIn this cohort, grade 3 and pT2 tumours predominated. The most common site for metastasis was the lung and pleura (41, 32.8%), and 15 (12.0%) cases demonstrated metastasis in multiple sites. Among these, 92% of tumours metastasised without preceding local recurrences. Five- and ten-year overall survival (OS) rates were 27% and 7.2%, while 5- and 10- year survival rates after metastasis were 9.6% and 3.2% respectively. AR, ERβ and p53 protein expressions were observed in 16%, 96.8% and 58.1% of tumours, respectively. A combinational phenotype of AR-ERβ+p53+ tumours was associated with poorer OS (HR 1.543, 95%CI 1.030 to 2.310, p=0.035). Higher AR mRNA levels were significantly associated with favourable OS (p=0.015) and survival after metastasis (p=0.027).ConclusionsMetastatic TNBC harboured aggressive behaviour and displayed predominantly visceral metastasis with most metastatic events occurring without intervening local recurrences. A combinational phenotype of AR-ERβ+p53+ was significantly associated with poorer OS.

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Section: Discussioncontrasting

confidence: 74%

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

Goto¹,

Thike

Ong

et al. 2019

J Clin Pathol

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“…The heterogeneity of breast cancer includes differences in ethnicity, menopausal status, ER/PR status, HER-2/neu expression, and other molecular signatures [30,31]. Finding the sources of breast cancer heterogeneity would contribute to subtype specific therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory receptor immunoglobulin-like transcript 4 was highly expressed in primary ductal and lobular breast cancer and significantly correlated with IL-10

et al. 2014

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BackgroundImmunoglobulin-like transcript 4 (ILT4) is an inhibitory molecule involved in immune response and has recently been identified to be strongly inducible by IL-10. The aim of the present study was to examine the associations of ILT4 expression with clinicopathological characteristics and IL-10 expression in primary ductal and lobular breast cancer.MethodsWe studied the expression of ILT4 in 4 cancer cell lines, 117 primary tumor tissues and 97 metastatic lymph nodes from patients with primary ductal and lobular breast cancer by reverse transcription-polymerase chain reaction, western blot or immunohistochemistry analysis. Additionally, IL-10 expression was also investigated using immunohistochemistry in primary tumor tissues. Then the relationship between ILT4 expression and clinicopathological characteristics/IL-10 expression was evaluated.ResultsILT4 was highly expressed in all 4 human breast cancer cell lines on both mRNA and protein levels. In primary tumor tissues, ILT4 or IL-10 was expressed in the cell membrane, cytoplasm, or both; the positive rate of ILT4 and IL-10 expression was 60.7% (71/117) and 80.34% (94/117), respectively. ILT4 level was significantly correlated with IL-10 (r =0.577; p < 0.01). Furthermore, the expression of ILT4 or IL-10 was associated with less number of Tumor Infiltrating Lymphocytes (TILs) (p = 0.004 and 0.018, respectively) and more lymph node metastasis (p = 0.046 and 0.035, respectively).ConclusionOur data demonstrated the association of ILT4 and IL-10 expression in human breast cancer, suggesting their important roles in immune dysfunction and lymph node metastases.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1692652692107916

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“…For example, the frequency of ERβ expression in breast tumors has been reported to range from 17-100% [ 15 , 18 , 21 – 35 ] and from 13-83% in ERα negative breast cancer [ 17 , 24 , 29 , 30 , 33 , 36 ]. With regard to the biological functions of ERβ, a number of studies have shown that the presence of this receptor correlates with improved rates of recurrence, disease-free survival and overall survival [ 22 , 24 – 27 , 37 – 41 ] while others indicate little to no correlation [ 28 , 30 , 38 ] or even worse prognosis [ 33 , 42 – 44 ]. Lastly, several studies have reported that the presence of ERβ in breast tumors increases the effectiveness of tamoxifen therapy [ 36 , 45 – 48 ] or aromatase inhibitor therapy [ 47 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer

et al. 2014

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BackgroundThe role and clinical value of ERβ1 expression is controversial and recent data demonstrates that many ERβ antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize ERβ1 expression across all sub-types of breast cancer using a validated antibody and determine the roles of this receptor in mediating response to multiple forms of endocrine therapy both in the presence and absence of ERα expression.MethodsNuclear and cytoplasmic expression patterns of ERβ1 were analyzed in three patient cohorts, including a retrospective analysis of a prospective adjuvant tamoxifen study and a triple negative breast cancer cohort. To investigate the utility of therapeutically targeting ERβ1, we generated multiple ERβ1 expressing cell model systems and determined their proliferative responses following anti-estrogenic or ERβ-specific agonist exposure.ResultsNuclear ERβ1 was shown to be expressed across all major sub-types of breast cancer, including 25% of triple negative breast cancers and 33% of ER-positive tumors, and was associated with significantly improved outcomes in ERα-positive tamoxifen-treated patients. In agreement with these observations, ERβ1 expression sensitized ERα-positive breast cancer cells to the anti-cancer effects of selective estrogen receptor modulators (SERMs). However, in the absence of ERα expression, ERβ-specific agonists potently inhibited cell proliferation rates while anti-estrogenic therapies were ineffective.ConclusionsUsing a validated antibody, we have confirmed that nuclear ERβ1 expression is commonly present in breast cancer and is prognostic in tamoxifen-treated patients. Using multiple breast cancer cell lines, ERβ appears to be a novel therapeutic target. However, the efficacy of SERMs and ERβ-specific agonists differ as a function of ERα expression.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-749) contains supplementary material, which is available to authorized users.

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Significance of ERβ expression in different molecular subtypes of breast cancer

Cited by 15 publications

References 21 publications

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

Inhibitory receptor immunoglobulin-like transcript 4 was highly expressed in primary ductal and lobular breast cancer and significantly correlated with IL-10

ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer

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