Oestrogen receptor-beta1 but not oestrogen receptor-betacx is of prognostic value in apocrine carcinoma of the breast.
ABSTRACT 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.
SourceAvailable from: Hatem A Azim[Show abstract] [Hide abstract]
ABSTRACT: Greater understanding of the biology of triple-negative breast cancer (TNBC) is needed to discern the roughly 60% of node-negative patients who are already cured with locoregional therapy from the 40% who need adjuvant systemic therapy to be cured. Recent evidence suggests that patients with TNBC whose tumours have an activated immune response gene signature have a more favourable outcome than TNBC patients without this signature. For the group who needs additional systemic therapy, the challenge remains to choose the right systemic drug combination for the right TNBC sub-type. Significant heterogeneity exists within the TNBC class that is exemplified by differing chemotherapeutic sensitivity observed for some sub-types. This heterogeneity establishes the need for identifying differentiating molecular markers within the overall class of TNBC disease, which may help refine therapeutic management. In this review, we discuss some of these promising predictive molecular markers for tailoring therapy. In addition, several gene expression profiling and functional studies employing genetic screens that help to establish TNBC sub-groups with varying sensitivities to a variety of targeted therapies currently under clinical investigation are conferred. It is anticipated that a greater understanding of the biology of TNBC and its complex heterogeneity will reveal novel targets or identify markers around which clinical trials in molecularly well-defined sub-groups can be designed.Annals of Oncology 08/2012; 23 Suppl 6:vi13-vi18. DOI:10.1093/annonc/mds188 · 6.58 Impact Factor
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ABSTRACT: Apocrine carcinoma of the breast is a rare, special type of breast carcinoma showing distinct morphologic, immunohistochemical and molecular genetic features. Apocrine epithelium has a characteristic steroid receptor profile that is estrogen receptor and progesterone receptor negative and androgen receptor positive. This combination of morphologic and immunohistochemical characteristics is essential for the proper recognition of the apocrine carcinomas. Strictly defined, apocrine carcinomas express either Her-2/neu or EGFR, which along with androgen receptor positivity make patients with the apocrine carcinoma eligible for targeted therapies.Histology and histopathology 06/2013; 28(11):1393-1409. · 2.24 Impact Factor
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ABSTRACT: Estrogen is essential for growth and development of the mammary glands and has been associated with the promotion and growth of breast cancer and in line with this, most human breast cancers are initially estrogen-dependent and undergo regression when deprived of their supporting hormone. Estrogen exerts many of its effects via two nuclear estrogen receptors (ERs), ERα and ERβ. The discovery of a second ER, ERβ, demanded a full re-evaluation of estrogen action in all target tissues and different estrogen associated diseases, including human breast cancer. However, despite over 15 years of research, the exact role, if any, of ERβ in human breast cancer remains elusive. The main challenges now are to develop highly selective anti-ERβ antibodies that are applied to large well characterized human breast cancer samples to validate their diagnostic potential and to explore ERβ-selective agonists in animal models of breast cancer to validate their therapeutic potential.Molecular and Cellular Endocrinology 01/2014; 382(1):665–672. DOI:10.1016/j.mce.2013.08.005 · 4.24 Impact Factor