The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

Chiodo, Chiara; Morelli, Catia; Cavaliere, F.; Sisci, Diego; Lanzino, Marilena

doi:10.3390/ijms23010424

Cited by 8 publications

(6 citation statements)

References 108 publications

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“…Androgens, such as testosterone and dihydrotestosterone, are known to augment sebum production and precipitate acne, 29 whereas their influence on breast cancer remains an area of debate and ongoing research. 30 Hormonal fluctuations pertinent to breast cancer could also modulate acne manifestation. Furthermore, the management of breast cancer with chemotherapeutic and targeted therapies introduces additional variables.…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Yang,

Zhao

2024

Skin Research and Technology

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IntroductionPrior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain.MethodsUtilizing a bidirectional two‐sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions—namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea—and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome‐wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR‐Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings.ResultsThe MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011–1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886–0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study's conclusions.ConclusionFindings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

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Section: Discussionmentioning

confidence: 99%

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Yang,

Zhao

2024

Skin Research and Technology

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“…One potential explanation is that progestin can interact with other receptors. NETA has some affinity for the androgen receptor [ 36 ] which have been shown to promote epithelial–mesenchymal transition, migration and invasiveness in positive triple-negative BC cell lines [ 37 ]. Progestin can also interact through progestin-induced paracrine signalling via the receptor activator of nuclear factor Kappa B (RANK) ligand (RANKL).…”

Section: Discussionmentioning

confidence: 99%

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

Støer,

Vangen,

Singh

et al. 2024

Br J Cancer

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Background It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. Methods We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. Results We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31–2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35–1.96) to Kliogest®: 2.67 (2.37–3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86–2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83–2.30) than screen-detected (HR 1.33, 95% CI 1.26–1.41) BC in women 50–71 years. HRs for HT use decreased with increasing BMI. Conclusions The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

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“…Although the presence of AR in normal and neoplastic breast tissues was revealed decades ago [6][7][8], only in recent years the role played by androgens/androgen receptor (AR) signaling in breast cancer growth and progression, prognosis, and treatment has gained much interest. Consequently, AR signaling has been analyzed, mainly for the definition of new tailored therapies [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Androgens Modulate Bcl-2 Agonist of Cell Death (BAD) Expression and Function in Breast Cancer Cells

Morelli,

Chiodo,

Nocito

et al. 2023

IJMS

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Androgen receptor (AR) expression in estrogen receptor-positive (ER+) breast cancer (BC) correlates with lower tumor grade and a better clinical outcome. Additionally, in normal mammary epithelium or ER+ BC preclinical models, androgens counteract basal/ER-dependent proliferation. Here, we report an additional mechanism, underlining the protective role exerted by AR. Specifically, the activation of intracellular AR upregulates the Bcl-2-family protein BAD, and TCGA database analyses show that in ER+ BC, BAD expression is associated with better disease-free survival. Ligand-activated AR influences its own and BAD cellular compartmentalization by enhancing levels in the nucleus, as well as in mitochondrial fractions. In both compartments, BAD exerts unconventional functions. In the nucleus, BAD and AR physically interact and, upon androgen stimulation, are recruited at the AP-1 and ARE sites within the cyclin D1 promoter region, contributing to explaining the anti-proliferative effect of androgens in BC cells. Androgens cause an enrichment in BAD and AR content in the mitochondria, correlated with a decrease in mitochondrial function. Thus, we have defined a novel mechanism by which androgens modulate BAD expression, its mitochondria localization, and nuclear content to force its ability to act as a cell cycle inhibitor, strengthening the protective role of androgen signaling in estrogen-responsive BCs.

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The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

Cited by 8 publications

References 108 publications

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Causal relationship between inflammatory skin diseases and breast cancer: A bidirectional Mendelian randomization study

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

Androgens Modulate Bcl-2 Agonist of Cell Death (BAD) Expression and Function in Breast Cancer Cells

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