Oestrogen receptor-β1 but not oestrogen receptor-βcx is of prognostic value in apocrine carcinoma of the breast

Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Apmis (Impact Factor: 2.04). 11/2008; 116(10):923-30. DOI: 10.1111/j.1600-0463.2008.01122.x
Source: PubMed


Apocrine carcinoma of the breast, which frequently expresses oestrogen receptor-beta (ER-beta) in the absence of ER-alpha and only infrequently is treated endocrinologically, gives an opportunity to investigate the clinicopathological role of ER-beta in breast cancer independent of ER-alpha expression or tamoxifen treatment. Several isotypes of ER-beta, ER-beta1-5 etc., have been identified thus far; however, the clinicopathological importance of each ER-beta isotype in breast cancer is still uncertain. Here we aimed to clarify the clinicopathological importance of ER-beta1 and ER-betacx (ER-beta2) in apocrine carcinomas, immunohistochemically examining expressions of ER-beta1 and ER-betacx in 47 apocrine carcinomas. Positivity for ER-beta1 and ER-betacx was observed in 41 (87%) and 18 (38%) of 47 cases, respectively. ER-beta1 positivity was related to smaller tumor size (P=0.0359), lower histological grade (P=0.0322), and higher disease-free survival (P<0.0001), whereas ER-betacx status was related to none of these parameters. ER-beta1 positivity was also associated with favorable clinical outcome in 24 so-called triple-negative (ER-alpha-negative/PR-negative/HER2-negative) apocrine carcinomas. ER-beta1 itself, independent of ER-alpha expression and tamoxifen treatment, seems to have a tumor-suppressive effect, at least in apocrine carcinomas. Further study of ER-beta1 is desired to optimize breast cancer treatment.

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    • "Eleven of the fourteen studies also studied ERb2. Five did not find a correlation of ERb2 with any clinical outcome or survival [12] [14] [56] [60] [63]. Two investigations showed ERb2 as a poor prognosticator [58] [64], whereas two others found ERb2 associated with better outcomes [59] [61]. "
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    ABSTRACT: Estrogen receptor (ER) β was discovered over a decade ago. The design of most studies on this receptor was based on knowledge of its predecessor, ERα. Although breast cancer (BCa) has been a main focus of ERβ research, its precise roles in breast carcinogenesis remain elusive. Data from in vitro models have not always matched those from observational or clinical studies. Several inherent factors may contribute to these discrepancies: (a) several ERβ spliced variants are expressed at the protein level, and isoform-specific antibodies are unavailable for some variants; (b) post-translational modifications of the receptor regulate receptor functions; (c) the role of the receptor differs significantly depending on the type of ligands, cis-elements, and co-regulators that interact with the receptor; and (d) the diversity of distribution of the receptor among intracellular organelles of BCa cells. This review addresses the gaps in knowledge in ERβ research as it pertains to BCa regarding the following questions: (1) is ERβ a tumor suppressor in BCa?; (2) do ERβ isoforms play differential roles in breast carcinogenesis?; (3) do nuclear signaling and extranuclear ERβ signaling differ in BCa?; (4) what are the consequences of post-translational modifications of ERβ in BCa?; (5) how do co-regulators and interacting proteins increase functional diversity of ERβ?; and (6) how do the types of ligand and regulatory cis-elements affect the action of ERβ in BCa?. Insights gained from these key questions in ERβ research should help in prevention, diagnosis/prognosis, and treatment of BCa.
    Steroids 03/2012; 77(7):727-37. DOI:10.1016/j.steroids.2012.03.008 · 2.64 Impact Factor
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    • "Two retrospective studies showed no associations of ERb2 expression with clinical outcome among women with invasive breast cancer and response to treatment [19] [25]. In immunohistochemistry (IHC)-based studies, ERb1 was of predictive value for tamoxifen response and of independent prognostic value [17] [19] [21]. On the contrary, other studies found only ERb2 variant to be of predictive value [20] [22]. "
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    ABSTRACT: In breast cancer, little is known about the consequences of co-expression of ERα with the second estrogen receptor, ERβ, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ERα and ERβ expression levels in breast tumors. To address whether the expression ratio of ERα and ERβ and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ERβ1 to ERβ2 and ERα in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. A specific correlation of ERβ1 expression levels with tumor size was detected in early-onset breast cancer patients and of ERβ2 levels with tumor size in late-onset patients. Expression of both ERβ isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ERβ2 than ERβ1 isoform were associated with a better outcome in late-onset patients. Our results suggest that different isoforms of ERβ may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values.
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