Is it time to consider the Androgen receptor as a therapeutic target in breast cancer?

2021 ◽  
Vol 21 ◽  
Author(s):  
Melika Kooshki Forooshani ◽  
Rosa Scarpitta ◽  
Giuseppe Nicolò Fanelli ◽  
Mario Miccoli ◽  
Antonio Giuseppe Naccarato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Prognostic Impact ◽  
Nuclear Receptor Superfamily ◽  
Cancer Pathogenesis ◽  
Novel Biomarkers ◽  
Tumorigenic Mechanism

: Breast cancer (BC) is a heterogeneous disease and the most prevalent malignant tumor in women worldwide. The majority of BC cases are positive for estrogen receptor (ER) and progesterone receptor (PgR), both known to be involved in cancer pathogenesis, progression, and invasion. In line with this, hormonal deprivation therapy appears to be a useful tool and an effective treatment for these BC subtypes. Unfortunately, prognosis among patients with hormone-negative tumors or therapy-refractory and metastatic patients remains poor. Novel biomarkers are urgently needed in order to predict the course of the disease, make better therapy decisions and improve the overall survival of patients. In this respect, the androgen receptor (AR), a member of the hormonal nuclear receptor superfamily and ER and PgR, emerges as an interesting feature widely expressed in human BCs. Despite the advances, the precise tumorigenic mechanism of AR and the role of its endogenous ligands are yet not well-understood. In this review, we aim to elaborate on the prognostic impact of AR expression and current AR-targeting approaches based on previous studies investigating AR's role in different BC subtypes.

Interferon Signaling in Estrogen Receptor-positive Breast Cancer: A Revitalized Topic

Endocrinology ◽  
2021 ◽  
Author(s):  
Xiaoyong Fu ◽  
Carmine De Angelis ◽  
Rachel Schiff
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Breast Cancer Subtype ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Cancer Pathogenesis ◽  
Estrogen Receptor Positive

Abstract Cancer immunology is the most rapidly expanding field in cancer research, with the importance of immunity in cancer pathogenesis now well accepted including in the endocrine-related cancers. The immune system plays an essential role in the development of ductal and luminal epithelial differentiation in the mammary gland. Originally identified as evolutionarily conserved anti-pathogen cytokines, interferons (IFNs) have shown important immune-modulatory and antineoplastic properties when administered to patients with various types of cancer including breast cancer. Recent studies have drawn attention to the role of tumor and stromal infiltrating lymphocytes in dictating therapy response and outcome of breast cancer patients, which, however, is highly dependent on the breast cancer subtype. The emerging role of tumor cell inherent IFN signaling in the subtype-defined tumor microenvironment could influence therapy response with protumor activities in breast cancer. Here we review evidence with new insights of tumor cell-intrinsic and tumor microenvironment-derived IFN signaling, and the crosstalk of IFN signaling with key signaling pathways in estrogen receptor-positive (ER+) breast cancer. We also discuss clinical implications and opportunities exploiting IFN signaling to treat advanced ER+ breast cancer.

The prognostic role of androgen receptor in early-stage breast cancer patients: A meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 528-528 ◽  
Author(s):  
Ivana Bozovic-Spasojevic ◽  
Dimitrios Zardavas ◽  
Evandro De Azambuja ◽  
Lieveke Ameye ◽  
Christos Sotiriou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Early Stage ◽  
Meta Analysis ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Prognostic Role ◽  
The Impact

528 Background: Androgen receptor (AR) expression has been observed in ~70% of breast cancer (BC) patients, but its prognostic role is not established yet. To assess this we performed a meta-analysis of studies that evaluated the impact of AR on disease free survival (DFS) and/or on overall survival (OS) in early stage BC. Methods: Published studies were identified by an electronic search on PubMed using the MeSH terms "breast neoplasm" and "androgen receptor" (up to June 2012). Identified studies were assessed against the following criteria for inclusion in the analysis: early stage BC and reported results of AR status in correlation with clinical outcome. We report combined HRs with 95% confidence intervals (CI) using AR negative patients as reference. Results: Twenty studies were eligible for the meta-analysis out of 493 initially identified and 12 among them, including 6,525 patients, were considered as evaluable (i.e., reporting enough information to allow aggregation of results). AR positivity was associated with lower risk of relapse in all breast cancer patients, and better overall survival in both univariate (U) and multivariate (M) analysis. AR prognostic impact in different subtypes was also assessed (see Table). Conclusions: Our analysis demonstrated that AR delivers prognostic information overall, serving as a positive prognostic factor in early stage BC. Further studies are needed to delineate its prognostic impact within the different subtypes of the disease. [Table: see text]

scholarly journals The Role of Nuclear Receptors in Prostate Cancer

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 602 ◽  
Author(s):  
Masaki Shiota ◽  
Naohiro Fujimoto ◽  
Eiji Kashiwagi ◽  
Masatoshi Eto
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Estrogen Receptor Α ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Functional Roles ◽  
Cancer Pathogenesis

The nuclear receptor (NR) superfamily consists of 48 members that are divided into seven subfamilies. NRs are transcription factors that play an important role in a number of biological processes. The NR superfamily includes androgen receptor, which is a key player in prostate cancer pathogenesis, suggesting the functional roles of other NRs in prostate cancer. The findings on the roles of NRs in prostate cancer thus far have shown that several NRs such as vitamin D receptor, estrogen receptor β, and mineralocorticoid receptor play antioncogenic roles, while other NRs such as peroxisome proliferator-activated receptor γ and estrogen receptor α as well as androgen receptor play oncogenic roles. However, the roles of other NRs in prostate cancer remain controversial or uninvestigated. Further research on the role of NRs in prostate cancer is required and may lead to the development of novel preventions and therapeutics for prostate cancer.

scholarly journals Hormone Receptor Expression in Multicentric/Multifocal versus Unifocal Breast Cancer: Especially the VDR Determines the Outcome Related to Focality

2019 ◽  
Vol 20 (22) ◽  
pp. 5740 ◽  
Author(s):  
Alaleh Zati zehni ◽  
Sven-Niclas Jacob ◽  
Jan-Niclas Mumm ◽  
Helene Hildegard Heidegger ◽  
Nina Ditsch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Vitamin D Receptor ◽  
Hormone Receptor ◽  
Receptor Expression ◽  
Prognostic Impact ◽  
Multifocal Breast Cancer

The aim of this study was to evaluate the prognostic impact that hormone receptor (HR) expressions have on the two different breast cancer (BC) entities—multifocal versus unifocal BC. As the prognosis determining aspects, we investigated the overall survival (OS) and disease-free survival (DFS) by univariate and multivariate analysis. To underline the study’s conclusions, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging. A retrospective analysis was performed on survival-related events in a series of 320 breast cancer patients treated at the Department of Gynecology and Obstetrics at the Ludwig Maximillian University in Munich between 2000 and 2002. All three steroid receptors analyzed by immunohistochemistry, namely, the estrogen receptor (ER), the progesterone receptor (PR), and the vitamin D receptor (VDR), showed a significantly positive influence on the course of the disease, but only for the unifocal breast tumor patients. The prognosis of patients with multifocal breast cancer was either not affected by estrogen and/or progesterone receptor expression or even involved a worse etiopathology for the vitamin D receptor-positive patients. The estrogen receptor in unifocal breast cancer and the vitamin D receptor in multifocal breast cancer were especially identified as an independent prognostic marker for overall survival, when adjusted for age, grading, and staging. Altogether, our results strengthen the need to further investigate the behavior of the hormone receptors in breast cancer and understand why they have different effects on each focality type. Moreover, the studies for an adopted vitamin D supplementation due to breast cancer focality type must be enlarged to fully comprehend the remarkable and interesting role played by the vitamin D receptor.

scholarly journals Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 543
Author(s):  
Rosaria Benedetti ◽  
Chiara Papulino ◽  
Giulia Sgueglia ◽  
Ugo Chianese ◽  
Tommaso De Marchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Mirna Expression ◽  
Estrogen Receptor Alpha ◽  
Estrogen Signaling ◽  
Integrated Analysis ◽  
Tumor Resistance ◽  
Estrogen Receptor Signaling

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

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