Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis

Yue, Wei; Yager, James D.; Wang, Ji Ping; Jupe, Eldon R.; Santen, Richard J.

doi:10.1016/j.steroids.2012.11.001

Cited by 194 publications

(170 citation statements)

References 47 publications

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“…High-dose exogenous cross-sex estrogens and androgen antagonists stimulate the formation of breast lobules, ducts, and acini histologically identical to those of biological females (43). Exogenous estrogen binds to the estrogen receptor in the breast tissue and is hypothesized to stimulate carcinogenesis via increased cell proliferation, decreased apoptosis, and elevated production of oxidative metabolites that result in DNA damage (76,77). Higher serum levels of endogenous estradiol have been associated with higher breast cancer risk in nontransgender natal males (78), lending further support to the hypothesis that transwomen may be at increased risk of breast cancer due to hormonal therapy.…”

Section: Possible Effects Of Cross-sex Hormonesmentioning

confidence: 99%

Cancer in Transgender People: Evidence and Methodological Considerations

Braun

Nash

Tangpricha

et al. 2017

Epidemiologic Reviews

168

122

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Transgender people comprise a diverse group of individuals whose gender identity or expression differs from that originally assigned to them at birth. Some, but not all, transgender people elect to undergo medical gender affirmation, which may include therapy with cross-sex hormones and/or surgical change of the genitalia and other sex characteristics. As cross-sex hormones administered for the purposes of gender affirmation may be delivered at high doses and over a period of decades, the carcinogenicity of hormonal therapy in transgender people is an area of considerable concern. In addition, concerns about cancer risk in transgender patients have been linked to sexually transmitted infections, increased exposure to well-known risk factors such as smoking and alcohol use, and the lack of adequate access to screening. Several publications have identified cancer as an important priority in transgender health research and called for large-scale studies. The goals of this article are to summarize the evidence on factors that may differentially affect cancer risk in transgender people, assess the relevant cancer surveillance and epidemiologic data available to date, and offer an overview of possible methodological considerations for future studies investigating cancer incidence and mortality in this population.

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Section: Possible Effects Of Cross-sex Hormonesmentioning

confidence: 99%

Cancer in Transgender People: Evidence and Methodological Considerations

Braun

Nash

Tangpricha

et al. 2017

Epidemiologic Reviews

168

122

View full text Add to dashboard Cite

show abstract

“…A causal relationship between ESR1 copy numbers and increased expression of ERα protein, which drives cell proliferation [9][10][11] , provides the molecular underpinning of the potential clinical relevance of ESR1 amplification. Expression of the ERα-protein itself has long been used for decades as a biomarker for initiating anti-estrogen treatment in breast cancer [9] .…”

Section: Gains For Expressionmentioning

confidence: 99%

“…ESR1 encodes the estrogen receptor alpha (ERα), which is a cellular receptor for the steroid hormone estrogen, a key molecule that regulates the growth and differentiation of the mammary gland [4][5][6][7][8] . ERα is activated by estrogen and drives cell proliferation in breast cancer [9][10][11] . About two thirds of breast cancers express ERα at the time of diagnosis, making the ERα-protein the most frequently applied clinical biomarker and molecular therapy target for this tumor type [9,[12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

Holst¹

2016

WJCO

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Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1 ) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1 , and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1 . This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.

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“…The most widely accepted theory holds that estradiol, acting through Estrogen Receptor Alpha (ERα), stimulates cell proliferation and initiates mutations arising from replicative errors occurring during pre-mitotic DNA synthesis. The promotional effects of estradiol then support the growth of cells harboring mutations [7]. Laboratory and epidemiological data also suggest that non-receptor mediated mechanisms resulting from the genotoxic effects of estrogen metabolites are involved in breast cancer development.…”

Section: Molecular Basis Of Hormonal Therapymentioning

confidence: 99%

Hormone Therapy in Breast Cancer: Where do We Stand?

Jandyal¹,

Bajpai²

2017

J Integr Oncol

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Breast cancer is not only the most common malignancy but also the leading causes of cancer-related deaths in women worldwide. The management of breast cancer is subtype driven and determination of hormone receptor [HR] status, a major driving force for the tumor growth is of paramount importance. The use of hormone therapy [HT] to treat HR positive breast cancer is practiced for more than a century and is one of the pivotal examples of precision medicine.The present perspective focuses on the state of the art hormone therapy for early and advanced breast cancer in both pre and post-menopausal women. Recent advances in HT strategies, with respect to single or combination therapy use, adding agents targeting HT resistance, checkpoint inhibitors, and optimal duration of endocrine therapy are also being addressed. Opportunities for individualized patient care are discussed.

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Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis

Cited by 194 publications

References 47 publications

Cancer in Transgender People: Evidence and Methodological Considerations

Cancer in Transgender People: Evidence and Methodological Considerations

Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

Hormone Therapy in Breast Cancer: Where do We Stand?

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