Effects of short-term estradiol and norethindrone acetate treatment on the breasts of normal postmenopausal women

Cheng, Guojun; Butler, Ryan; Warner, Margaret; Gustafsson, Jan Åke; Wilczek, Brigitte; Landgren, B.-M.

doi:10.1097/gme.0b013e318276c4ea

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…Eighty-three percent of the ERβ2-positive samples were from postmenopausal women, and in all of these breasts there was abundant dense collagen, a condition that we have previously shown is correlated with mammographic diagnosis of dense breasts (36) (Fig. 4 E and F).…”

Section: Resultsmentioning

confidence: 97%

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Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer

Huang

Omoto

Iwase

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The role of estrogen receptor (ER) α as a target in treatment of breast cancer is clear, but those of ERβ1 and ERβ2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ERα was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ERβ. We found that whereas ductal cancer is a highly proliferative, ERα-positive, ERβ-negative disease, lobular cancer expresses both ERα and ERβ but with very few Ki67-positive cells. ERβ2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ERβ2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1α. ERβ2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERα nor ERβ was expressed, but in the high-grade lobular cancer ERβ was lost and ERα and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ERβ agonists in preventing in situ ductal cancers from becoming invasive.ductal carcinoma in situ | invasive ductal carcinoma | invasive lobular carcinoma

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Section: Resultsmentioning

confidence: 97%

“…As was shown recently (36), density of collagen is a histological marker of breast density. In the present study there was a marked correlation between expression of ERβ2 and breast density as measured by collagen staining.…”

Section: Discussionmentioning

confidence: 95%

Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer

Huang

Omoto

Iwase

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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149

120

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“…Most of the effects of 17β-Estradiol (E2) are mediated through its two nuclear receptors: ERα (ERα) and β (ERβ), which are encoded by different genes, ESR1 encodes ERα on chromosome 6 and ESR2 encodes ERβ on chromosome 14 [23,24]. ERβ is more abundant than ERα in normal human and mouse mammary gland [3,9,25] and both receptors contain in their structure different domains: Two ligand-independent transcriptional activation, N-terminal domains, NTD (A/B domains), also called activation factor 1 (AF1) domains, where MAPKs-mediated phosphorylation is carried out, a DNA-binding domain, DBD (C domain), a nuclear localization and heat shock proteins binding domain (domain D), a ligand-dependent transcriptional activation, ligand binding domain, LBD (domain E), also called activation factor 2 (AF2) domain and a C-terminal domain (domain F), which modulates the transcriptional activation mediated by domains A/B and E [3,26,27,28] (Figure 1). …”

Section: Estrogen Receptors (Erα and Erβ)mentioning

confidence: 99%

Tamoxifen Resistance: Emerging Molecular Targets

Rondón-Lagos

Villegas

Rangel

et al. 2016

IJMS

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17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM’s biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein—coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.

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“…In the adult gland, in both rodents (Saji et al 2000) and women (Cheng et al 2013), ERa is expressed in !10% of mammary epithelial cells. ERb is expressed in 70-80% of the mammary epithelial cells and is also expressed in the stroma and immune cells resident in the breast (Clarke et al 1997, Speirs et al 2002.…”

Section: Breast and Ermentioning

confidence: 99%

“…In addition to being a key player in reparation of double stranded breaks in DNA (Sun et al 2010), Tip60 is an interesting coactivator in the relationship between ERb and AR: TIP60 is an AR coactivator (reviewed in Culig & Santer (2012) and a facilitator of AR transport into the nucleus (Shiota et al 2010)). If in the absence of E 2 , ERb activation at AP1 sites causes proliferation, then the breasts of postmenopausal women should be proliferating but they are not (Cheng et al 2013), and ERb could increase proliferation in the prostate but it does not (Attia & Ederveen 2012). Clearly a more detailed analysis of the expression of coactivators in the breast and prostate is needed.…”

Section: Introductionmentioning

confidence: 99%

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

Dey¹,

Barros

Warner

et al. 2013

Journal of Molecular Endocrinology

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Estrogen and its receptors (ERs) influence many biological processes in physiology and pathology in men and women. ERs are involved in the etiology and/or progression of cancers of the prostate, breast, uterus, ovary, colon, lung, stomach, and malignancies of the immune system. In estrogen-sensitive malignancies, ERb usually is a tumor suppressor and ERa is an oncogene. ERb regulates genes in several key pathways including tumor suppression (p53, PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45 Skp2 , cMyc, and cyclin E);cell-cycle arresting factors (p21 WAF1

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Effects of short-term estradiol and norethindrone acetate treatment on the breasts of normal postmenopausal women

Abstract: This short-term prospective study shows that E2 and estrogen-progestogen treatment can up-regulate PRs but do not significantly affect ERs, AR, proliferation, or breast density.

Cited by 8 publications

References 29 publications

Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer

Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer

Tamoxifen Resistance: Emerging Molecular Targets

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

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