THE ROLE OF THE ANDROGEN RECEPTOR IN PRIMARY BREAST CANCER IN OLDER WOMEN

Abstract Aims Breast cancer in older women has more favourable biology, compared to younger women. Increased glutamine metabolism is a hallmark of cancer. The prognostic role of amino acid transporters involved with glutamine flux, SLC1A5 and SLC3A2, has been shown in breast cancer in younger women. This study aimed to investigate the role of SLC1A5 and SLC3A2 in breast cancer in older women as possible prognostic markers. Methods Surgical specimens were obtained from an existing series of 1,758 older women (≥70 years) with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 cases. Immunohistochemical staining for SLC1A5 and SLC3A2 was performed. H-score was considered as a continuous variable as well as using positivity cut-offs of ≥ 45 for SLC1A5 and ≥15 for SLC3A2, using X-tile software. Association between H-score and tumour size, grade, ER status, local-recurrence-free-survival (LRFS), overall survival (OS) and breast-cancer-specific-survival (BCSS) was investigated. Results No correlation was seen between neither marker and LRFS, OS, or BCSS in older women with breast cancer. Both markers were associated with high tumour grade and negative ER status (both p < 0.001). Conclusions These findings are contrary to those found in younger women, where these amino acid transporters are associated with shorter BCSS. This may suggest that breast cancer in older women is less reliant on glutamine metabolism, which is consistent with an overall less aggressive phenotype.

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Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000443052 ◽

2016 ◽

Vol 38 (3) ◽

pp. 1003-1014 ◽

Cited By ~ 24

Author(s):

Aiyu Zhu ◽

Yan Li ◽

Wei Song ◽

Yumei Xu ◽

Fang Yang ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Cyclin D1 ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211201150818 ◽

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.

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The role of androgen receptor in breast cancer

Drug Discovery Today Disease Mechanisms ◽

10.1016/j.ddmec.2012.11.003 ◽

2012 ◽

Vol 9 (1-2) ◽

pp. e19-e27 ◽

Cited By ~ 25

Author(s):

Domenico Iacopetta ◽

Yassine Rechoum ◽

Suzanne A.W. Fuqua

Keyword(s):

Breast Cancer ◽

Androgen Receptor

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Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients

Journal of Breast Cancer ◽

10.4048/jbc.2020.23.e28 ◽

2020 ◽

Vol 23 (2) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Yaewon Yang ◽

Ahrum Min ◽

Kyung-Hun Lee ◽

Han Suk Ryu ◽

Tae-Yong Kim ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Cancer Patients ◽

Early Breast Cancer ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Breast Cancer Patients ◽

Prognostic Role

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5th Symposium on Primary Breast Cancer in Older Women

Future Oncology ◽

10.2217/fon-2019-0070 ◽

2019 ◽

Vol 15 (7s) ◽

Keyword(s):

Breast Cancer ◽

Older Women ◽

Primary Breast Cancer

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The role of low keV virtual monochromatic imaging in increasing the conspicuity of primary breast cancer in dual-energy spectral thoracic CT examination for staging purposes

Acta Radiologica ◽

10.1177/0284185119858040 ◽

2019 ◽

Vol 61 (2) ◽

pp. 168-174 ◽

Cited By ~ 3

Author(s):

Yavuz Metin ◽

Nurgül Orhan Metin ◽

Oğuzhan Özdemir ◽

Filiz Taşçı ◽

Sibel Kul

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Energy Levels ◽

Iodine Content ◽

Pectoral Muscle ◽

Dual Energy ◽

Normal Breast

Background The additive value of dual-energy spectral computerized tomography (DESCT) in breast cancer imaging is still unknown. Purpose To investigate the role of DESCT in improving the conspicuity of primary breast cancer. Material and Methods Twenty-nine patients who were histopathologically diagnosed with breast cancer and underwent DESCT for staging of lung metastasis were evaluated retrospectively. The visual conspicuity of breast cancer was scored by two readers separately in reconstructed virtual monochromatic images obtained at 40, 60, 80, and 100 keV. A circular region of interest slightly smaller than the maximum contrasted portion of the primary breast cancer was manually placed. Iodine enhancement (HU) and iodine content (mg/mL) values of tumor, normal breast tissue and pectoral muscle, and contrast-to-noise values of images at four different energy levels were calculated. Results The lesion conspicuity score peaked at 40-keV series for both readers and was significantly higher than those at other energy levels (all P < 0.001). Lesion iodine enhancement was highest at 40-keV virtual monochromatic image reconstructions ( P < 0.001). The iodine content was significantly higher in tumor than normal breast tissue, and pectoral muscle ( P < 0.001). The highest contrast-to-noise value was obtained at 60 keV (4.0 ± 2.5), followed by 40 keV (3.9 ± 2.2), without a significant difference ( P = 0.33). Conclusion The conspicuity of primary breast cancer was significantly higher in low keV virtual monochromatic images obtained by DESCT. This gives us hope that DESCT may play an effective role in detecting incidental breast lesions. It also raises the question of whether quantitative values obtained by DESCT can be used for characterization of primary breast lesion.

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