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

Litwiniuk, Maria; Rożnowski, Krzysztof; Filas, Violetta; Godlewski, Dariusz; Stawicka, Małgorzata; Kaleta, Remigiusz; Bręborowicz, J

doi:10.1186/1471-2407-8-100

Cited by 33 publications

(28 citation statements)

References 38 publications

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“…This is similar to 84% (94% BRCA1, 75% BRCA2 and 81% BRCAX) obtained by Daidone et al [19] and higher than 42% reported in a series of 48 patients with founder BRCA1 mutation [20]. Although potentially due to differing patient cohorts, the discrepancy with the latter study may be due to their use of a different polyclonal antibody.…”

Section: Discussioncontrasting

confidence: 50%

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Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers

Yan

Rayoo²,

Takano

et al. 2010

Breast Cancer Res Treat

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Estrogen receptor (ER) α has been studied extensively in familial breast cancers but there are limited data on ERβ and its isoforms. This is an important issue since many BRCA1-associated tumours are "triple negative" and are resistant to conventional and targeted therapies. We performed an immunohistochemical study of pan-ERβ, ERβ1 and ERβ2 in a cohort of 123 familial breast carcinomas (35 BRCA1, 33 BRCA2 and 55 BRCAX) using a cut-off for positivity at 20% (Shaaban et al. in Clin Cancer Res 14:5228-5235, 2008). BRCA1 cancers were more likely to be nuclear ERα negative and nuclear pan-ERβ positive (21/32, 66%) when compared with BRCA2 (2/29, 7%) and BRCAX cancers (11/49, 22%) (both P < 0.001). For survival analysis, expression was also stratified using cut-offs defined by Bates et al. (Breast Cancer Res Treat 111:453-459, 2008) (score out of 7). Cytoplasmic ERβ2 expression correlated with shorter overall survival at 15 years regardless of cut-off used (both P < 0.046) At a cut-off score of 6 out of 7, cytoplasmic ERβ2 expression correlated with a poorer response to chemotherapy in both univariate (P = 0.011) and multivariate analyses including grade, lymph node status and chemotherapy as an interaction variable (P = 0.045, Hazard ratio 1.22, 95% CI 1.004-9.87). A similar trend was seen in a univariate analysis with a cut-off of 20% although this did not reach statistical significance (P = 0.057). Expression of nuclear ERβ1 was associated with a favourable response to endocrine therapy at 15 years regardless of cut-offs employed (both P < 0.025). However, this did not reach statistical significance in a multivariate analysis (P > 0.05). Since a significant proportion of ERα negative familial breast carcinomas are positive for nuclear ERβ1 and cytoplasmic ERβ2, the different ERβ isoforms and their intracellular location may need to be assessed, to identify patients that may benefit from hormonal and chemotherapy.

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Section: Discussioncontrasting

confidence: 50%

“…The first study in 44 familial cancer patients (16 BRCA1, 12 BRCA2 and 16 BRCAX) [19] and the second in 48 patients with BRCA1 founder mutation positive women [20]. However, there are no data regarding the range of expression for its different isoforms and the cellular pattern of expression for either BRCA1-or BRCA2-associated tumours.…”

Section: Introductionmentioning

confidence: 99%

Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers

Yan

Rayoo²,

Takano

et al. 2010

Breast Cancer Res Treat

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“…This suggests that other mediators are involved in regulation of estrogen’s effects in these patients. Litwiniuk et al [46] examined ERα, ERβ and PR in 48 women with mutations in BRCA1 gene and in a control group of 120 breast cancer samples using antibodies for ERα, PR and ERβ. Their data revealed that only 14.5% of BRCA1-related cancers expressed ERα compared with 57.5% in the control group.…”

Section: Existence Of E2/erβ-mediated Signaling Pathways In Tn-brementioning

confidence: 99%

“…Mandusic et al [46] measured the expression of ERβ1 and ERβ5 mRNAs in the 60 breast cancer samples and correlated their expression with ERα and PR protein levels with clinical/histopathological parameters. They found an inverse correlation between ERβ5 expression and the levels of ERα and PR proteins in postmenopausal patients.…”

Section: Existence Of E2/erβ-mediated Signaling Pathways In Tn-brementioning

confidence: 99%

“…While BRCA-1 and BRCA-2 are able to interact with ERα and regulate its transcriptional activities, a large fraction of BRCA-associated breast cancer patients are negative to ERα but expresse significant levels of ERβ[46, 80]. Thus, the effects of estrogens in these breast cancer patients might be largely mediated via ERβ.…”

Section: Interactions Of Erβ With Brca1/brca2 In Tn Breast Cancer mentioning

confidence: 99%

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ERα-negative and triple negative breast cancer: Molecular features and potential therapeutic approaches

Chen

Russo

2009

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

118

104

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Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential therapeutic approaches based on these features for TNBC, with particular focus on: 1) the pathological features of TNBC/basal-like breast cancer; 2) E2/ERβ – mediated signaling pathways; 3) G-protein coupling receptor-30/epithelial growth factor receptor (GPCR-30/EGFR) signaling pathway; 4) interactions of ERβ with breast cancer 1/2 (BRCA1/2); 5) chemokine CXCL8 and related chemokines; 6) altered microRNA signatures and suppression of ERα expression/ERα-signaling by micro-RNAs; 7) altered expression of several pro-oncongenic and tumor suppressor proteins; and 8) genotoxic effects caused by oxidative estrogen metabolites. Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC.

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BRCA1‐associated mammary tumorigenesis is dependent on estrogen rather than progesterone signaling

Ven

Liu

Burg

et al. 2018

The Journal of Pathology

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Hereditary breast cancers in BRCA1 mutation carriers are mostly estrogen receptor α (ERα)-negative and progesterone receptor (PR)-negative; however, hormone depletion via bilateral oophorectomy does result in a marked reduction in breast cancer risk, suggesting that BRCA1-associated breast tumorigenesis is dependent on hormone signaling. We used geneticaly engineered mouse models to determine the individual influences of ERα and PR signaling on the development of BRCA1-deficient breast cancer. In line with the human data, BRCA1-deficient mouse mammary tumors are ERα-negative, and bilateral ovariectomy leads to abrogation of mammary tumor development. Hormonal replacement experiments in ovariectomized mice showed that BRCA1-deficient mammary tumor formation is promoted by estrogen but not by progesterone. In line with these data, mammary tumorigenesis was significantly delayed by the selective ERα downregulator fulvestrant, but not by the selective PR antagonist Org33628. Together, our results illustrate that BRCA1-associated tumorigenesis is dependent on estrogen signaling rather than on progesterone signaling, and call into question the utility of PR antagonists as a tumor prevention strategy for BRCA1 mutation carriers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

Cited by 33 publications

References 38 publications

Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers

Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers

ERα-negative and triple negative breast cancer: Molecular features and potential therapeutic approaches

BRCA1‐associated mammary tumorigenesis is dependent on estrogen rather than progesterone signaling

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