Expression of wild‐type estrogen receptor β protein in human breast cancer: Specific correlation with HER2/<i>neu</i> overexpression

Umekita, Yoshihisa; Souda, Masakazu; Ohi, Yasuyo; Sagara, Yoshiatsu; Rai, Yoshiaki; Takahama, Tetsuya; Yoshida, Hiroki

doi:10.1111/j.1440-1827.2006.01983.x

Cited by 27 publications

(42 citation statements)

References 18 publications

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“…In contrast, there is a positive association between ERβ and HER2 expression in high-grade ERα-breast cancer [98]. In invasive ductal carcinoma, HER2 overexpression correlates inversely with ERα levels, but positively with ERβ [90]. Thus, ERα−/ERβ+ tumors tend to express HER2 but not PR, whereas ERα+/ERβ+, like ERα+/ERβ− tumors, tend to express PR but not HER2.…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 90%

“…Studies examining correlations between ERβ and PR have reported either no correlation [88,89], a weak positive correlation [81,90], or an inverse correlation [91]. One confounding variable for interpreting these studies is that there are two populations of tumors -one containing ERβ only, and another expressing both ERα and ERβ, which may have different phenotypes.…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

“…In general, HER2 gene amplification and protein overexpression are inversely correlated with expression of ERα, or with ERα and ERβ together [63,90,[94][95][96][97]. Some ER+ tumors have been shown to have HER2 gene amplification, and patients treated with TAM whose tumors are HER2+/ER+ have poorer disease-free survival (DFS) and overall survival (OS) than those without HER2 [10,96].…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

“…However, the correlation between ERβ expression and invasiveness is less clear. Although numerous researchers found no significant correlation between ERβ protein expression and tumor grade [81,82,88,90,95,97,98,[101][102][103][104], several groups showed that ERβ expression significantly correlates with low tumor grade [63,80,105] or in one case higher histological grade [89]. In these studies, all ERβ-containing tumors were analyzed together and included ERα+/ERβ+ (the majority) as well as ERα−/ERβ+ tumors.…”

Section: Clinical Correlations Between Erβ Expression Proliferationmentioning

confidence: 99%

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ERβ in breast cancer—Onlooker, passive player, or active protector?

2008

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The role of estrogen exposure in breast cancer risk is well-documented, and both estrogen synthesis and actions through the estrogen receptor (ER) have been targeted by therapies to control hormonedependent breast cancer. The discovery of a second ER form and its therapeutic implications sparked great interest. Both the original ERα and the more recently identified ERβ subtypes bind and respond similarly to many physiological and pharmacological ligands. However, differences in phytoestrogen binding have been noted, and subtype-specific ligands have been developed. Cell-based assays show that ERβ and its variants are generally less active on gene transcription than ERα, and may influence ERα activity; however, both gene-and cell-specific responses occur, and nongenomic activities are less well explored. Specific ligands, and methods to disrupt or eliminate receptor subtype expression in animal and cell models, demonstrate that the ERs have both overlapping and distinct biological functions. Overall, in cell-based studies, ERα appears to play a predominant role in cell proliferation, and ERβ is suggested to be antiproliferative.The potential for distinct populations of breast tumors to be identified based on ER subtype expression, and to exhibit distinct clinical behaviors, is of greatest interest. Several studies suggest that the majority of ER-positive tumors contain both subtypes, but that some tumors contain only ERβ and may have distinct clinical behaviors and responses. Expression of ERβ together with ERα favors positive responses to endocrine therapy in most studies, and additional studies to determine if the addition of ERβ to ERα as a tumor marker is of clinical benefit are warranted. In contrast, the positive association between ERβ and HER2 expression in high-grade ERα-negative breast cancer does not favor positive responses to endocrine therapy. Expression of ERβ in specific clinical subpopulations, and the potential for therapies targeting ERβ specifically, is discussed.

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Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 90%

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

Section: Clinical Correlations Between Erβ Expression Proliferationmentioning

confidence: 99%

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ERβ in breast cancer—Onlooker, passive player, or active protector?

2008

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“…24,25 Some studies demonstrated that HER2/neu breast cancers have elevated IL-8 expression and showed a correlation between HER2 and ERβ expression. 26,27 Based on these findings, the authors proposed the existence of a possible HER2/ERβ/IL-8 expression axis. To test this hypothesis, the authors first performed immunohistochemical staining on breast cancer clinical samples and found a positive association between IL-8 and ERβ.…”

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confidence: 99%

A new perspective on Estrogen Receptor beta in breast cancer progression

Han

2011

Cancer Biology & Therapy

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Biomarkers for the clinical management of breast cancer: International perspective

Patani

Martin

Dowsett

2013

Intl Journal of Cancer

154

113

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The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programmes and advances in adjuvant therapy. Optimal systemic management requires consideration of clinical, pathological and biological parameters. Oestrogen receptor alpha (ERa), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) are established biomarkers evaluated at diagnosis, which identify cardinal subtypes of breast cancer. Their prognostic and predictive utility effectively guides systemic treatment with endocrine, anti-HER2 and chemotherapy. Hence, accurate and reliable determination remains of paramount importance. However, the goals of personalized medicine and targeted therapies demand further information regarding residual risk and potential benefit of additional treatments in specific circumstances. The need for biomarkers which are fit for purpose, and the demands placed upon them, is therefore expected to increase. Technological advances, in particular high-throughput global gene expression profiling, have generated multi-gene signatures providing further prognostic and predictive information. The rational integration of routinely evaluated clinico-pathological parameters with key indicators of biological activity, such as proliferation markers, also provides a ready opportunity to improve the information available to guide systemic therapy decisions. The additional value of such information and its proper place in patient management is currently under evaluation in prospective clinical trials. Expanding the utility of biomarkers to lower resource settings requires an emphasis on cost effectiveness, quality assurance and possible international variations in tumor biology; the potential for improved clinical outcomes should be justified against logistical and economic considerations.

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Expression of wild‐type estrogen receptor β protein in human breast cancer: Specific correlation with HER2/neu overexpression

Cited by 27 publications

References 18 publications

ERβ in breast cancer—Onlooker, passive player, or active protector?

ERβ in breast cancer—Onlooker, passive player, or active protector?

A new perspective on Estrogen Receptor beta in breast cancer progression

Biomarkers for the clinical management of breast cancer: International perspective

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