A physiologic role for testosterone in limiting estrogenic stimulation of the breast

Dimitrakakis, Constantine; Zhou, Jian; Wang, Jie; Bélanger, Alain; Labrie, Fernand; Cheng, Chun; Powell, Douglas; Bondy, Carolyn A.

doi:10.1097/01.gme.0000055522.67459.89

Cited by 160 publications

(132 citation statements)

References 39 publications

(39 reference statements)

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“…Mechanistic evidence indicates that testosterone inhibits proliferation and stimulates apoptosis in breast epithelium (82,83). Analyses of observational data from the Women's Health Initiative study also showed that rates of estrogen receptor-negative breast cancer are inversely associated with circulating testosterone levels (80).…”

Section: Possible Effects Of Cross-sex Hormonesmentioning

confidence: 99%

“…The role of testosterone in breast cancer is not clear. Some studies have suggested that testosterone may reduce proliferation and increase apoptosis by decreasing the expression of estrogen receptor in breast epithelium (82,83). On the other hand, an increased risk of breast cancer has been reported with increased serum testosterone levels in both pre-and postmenopausal women (89)(90)(91).…”

Section: Possible Effects Of Cross-sex Hormonesmentioning

confidence: 99%

See 1 more Smart Citation

Cancer in Transgender People: Evidence and Methodological Considerations

Braun

Nash

Tangpricha

et al. 2017

Epidemiologic Reviews

163

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%

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

163

122

View full text Add to dashboard Cite

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“…Ar knockout transgenic models generally indicate that AR is required for normal mammary gland development (reviewed by Hickey et al (2012), Chang et al (2013) and Tarulli et al (2014)). In the human, AR appears to have a protective role in normal breast at least in part by opposing ERa action (Dimitrakakis et al 2003, Eigeliene et al 2012, Ochnik et al 2014. This raises the possibility of SARMs being used for breast cancer chemoprevention strategies in women with a high breast cancer risk.…”

Section: Conclusion/future Directionsmentioning

confidence: 99%

Complexities of androgen receptor signalling in breast cancer

McNamara¹,

Moore²,

Hickey³

et al. 2014

Endocrine-Related Cancer

123

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While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism has also been discussed and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR-directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.

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“…In the breast tissue, testosterone is converted either to dihydrotestostone (DHT) by 5α-reductase or to 17β-estradiol (E2) by aromatase and can function as an AR or ERα agonist respectively, thus having a dichotomous effect on breast development (8,15). Studies have shown that testosterone is converted to E2 under estrogen deprivation, but is preferentially metabolized into DHT when both hormones are present at physiological levels, thus hampering the E2-induced effects (16,17). Maintenance of this balance ensures the physiological response of the mammary gland depending on the hormonal needs and the menopausal status.…”

Section: The Androgen-ar Axis In Normal and Cancerous Breast Tissuementioning

confidence: 99%

“…The high histological and molecular diversity of the heterogeneous diseases comprising ER -BrCa may partially explain the inconclusive results regarding the prognostic value of AR in this molecular subtype of the disease (49). In addition, in the absence of ER (ER-tumors), testosterone may preferentially be metabolized into DHT rather than E2, leading to more potent ARstimulation (8,16,17). On the other hand, AR has been associated with HER-2 overexpression in ER -tumors (63).…”

Section: Ar As a Potential Biomarker In Breast Tumorsmentioning

confidence: 99%

The Role of the Androgen Receptor Signaling in Breast Malignancies

Christopoulos

Vlachogiannis

Vogkou

et al. 2017

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Abstract. Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed inBreast cancer (BrCa) is the most common solid tumor among women with an annual incidence of 123 new cases/100,000 females according to the United States Cancer Statistics and 252.710 estimated new cases in the U.S. in 2017. Despite significant progress made in therapeutics during the last 2 decades, BrCa still has a poor prognosis with 5-year survival rates of metastatic disease reaching to 26% only. BrCa is the second leading cause of death among female cancers with 40,610 estimated deaths in the U.S. expected in 2017 (1).Breast cancer comprises a heterogeneous group of diseases with variable course and outcome. Currently, BrCa is subclassified into distinct molecular subtypes named: normal breast like, luminal A/B, HER-2 related, basal-like and claudinlow (2, 3). Estrogen receptor (ER), progesterone receptor (PR) and HER2 have long been established as useful prognostic and predictive biomarkers. Hormonal therapy in ER and PR positive tumors (4), as well as the use of monoclonal antibodies in HER2 over-expressing tumors (5) have shown promising results, however overall survival of metastatic disease remains relatively low (1). To date, androgen receptor (AR) has been suggested to play a key role in breast cancer biology in certain disease subgroups (6, 7).AR is expressed in all stages of breast cancer (in-situ, primary and metastatic disease) and its contribution to the progression of disease may differ depending on the stage (8). Overall, AR expression among patients with breast cancer has been estimated at approximately 77% and varies significantly among molecular subtypes of BrCa (9). Human observational studies have associated AR with better outcome in ER + tumors, but this positive effect may be lost in ER-tumors (10, 11). Of interest, AR expression correlates with better clinicopathological features in the most aggressive form of BrCa, triple-negative breast cancer (TNBC) (12). AR seems to have distinct roles in disease development and progression depending on the tumor's hormonal environment and specifically upon relative levels of androgens and estrogens.The historically used androgens together with antiandrogens, Selective AR Modulators (SARMs) and Androgen Receptor antagonists constitute valuable options for the treatment of specific disease subpopulations. In the past decade, a wealth body of studies have focused on AR targeting along with hampering major signaling pathways 6533 This Αrticle is freely accessible online.

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A physiologic role for testosterone in limiting estrogenic stimulation of the breast

Abstract: These findings suggest that treatment with a balanced formulation including all ovarian hormones may prevent or reduce estrogenic cancer risk in the treatment of girls and women with ovarian failure.

Cited by 160 publications

References 39 publications

Cancer in Transgender People: Evidence and Methodological Considerations

Cancer in Transgender People: Evidence and Methodological Considerations

Complexities of androgen receptor signalling in breast cancer

The Role of the Androgen Receptor Signaling in Breast Malignancies

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