scholarly journals Co-Expression of Androgen Receptor and Cathepsin D Defines a Triple-Negative Breast Cancer Subgroup with Poorer Overall Survival

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1244 ◽  
Author(s):  
Hanane Mansouri ◽  
Lindsay B. Alcaraz ◽  
Caroline Mollevi ◽  
Aude Mallavialle ◽  
William Jacot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Cathepsin D ◽  
Triple Negative ◽  
Staining Intensity ◽  
Macrophage Infiltration ◽  
Receptor Subtype ◽  
Breast Cancer Subgroup

Background: In the triple-negative breast cancer (TNBC) group, the luminal androgen receptor subtype is characterized by expression of androgen receptor (AR) and lack of estrogen receptor and cytokeratin 5/6 expression. Cathepsin D (Cath-D) is overproduced and hypersecreted by breast cancer (BC) cells and is a poor prognostic marker. We recently showed that in TNBC, Cath-D is a potential target for antibody-based therapy. This study evaluated the frequency of AR/Cath-D co-expression and its prognostic value in a large series of patients with non-metastatic TNBC. Methods: AR and Cath-D expression was evaluated by immunohistochemistry in 147 non-metastatic TNBC. The threshold for AR positivity (AR+) was set at ≥1% of stained cells, and the threshold for Cath-D positivity (Cath-D+) was moderate/strong staining intensity. Lymphocyte density, macrophage infiltration, PD-L1 and programmed cell death (PD-1) expression were assessed. Results: Scarff-Bloom-Richardson grade 1–2 and lymph node invasion were more frequent, while macrophage infiltration was less frequent in AR+/Cath-D+ tumors (62.7%). In multivariate analyses, higher tumor size, no adjuvant chemotherapy and AR/Cath-D co-expression were independent prognostic factors of worse overall survival. Conclusions: AR/Cath-D co-expression independently predicted overall survival. Patients with TNBC in which AR and Cath-D are co-expressed could be eligible for combinatory therapy with androgen antagonists and anti-Cath-D human antibodies.

scholarly journals A Machine Learning Approach to Differentiate Two Specific Breast Cancer Subtypes Using Androgen Receptor Pathway Genes

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Taobo Hu ◽  
Guiyang Zhao ◽  
Yiqiang Liu ◽  
Mengping Long
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Histological Subtypes ◽  
Metaplastic Breast Cancer ◽  
Cancer Subtypes ◽  
Machine Learning Approach

Triple-negative breast cancer is a heterogeneous disease with different molecular and histological subtypes. The Androgen receptor is expressed in a portion of triple-negative breast cancer cases and the activation of the androgen receptor pathway is thought to be a molecular subtyping signature as well as a therapeutic target for triple-negative breast cancer. Thus, identification of the androgen receptor pathway status is important for both molecular characterization andclinical management. In this study, we investigate the expression of the androgen receptor pathway in metaplastic breast cancer and luminal androgen receptor subtypes of triple-negative breast cancer and found that the androgen receptor pathway was downregulated in metaplastic breast cancer compared to luminal androgen receptor subtype. Using random forest, we found that the two subtypes of breast cancer can be molecularly classified with the gene expression of the androgen receptor pathway.

Impact of androgen receptor on chemotherapy efficacy in patients with metastatic triple negative breast cancer

2020 ◽  
pp. 80-84
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

The objective: was to determine the impact of androgen receptor (AR) expression on the effectiveness of the first and second line chemotherapy in patients with metastatic triple negative breast cancer (mTNBC). Materials and methods. The impact of AR expression on treatment results was evaluated in patients with mTNBC received the first (n=122) and second (n=87) line chemotherapy in open randomized studies. The status of AR was evaluated by immunohistochemistry, AR positive patients were defined as having AR more than 10%. Results. From 116 patients with mTBNC 44 (38%) were AR positive, 72 (62%) – AR negative. Median progression free survival in patients received the first line chemotherapy was 8 months in AR positive and 6 months in AR negative, p=0.27. The incidence of objective tumor response in mTNBC patients received the second line chemotherapy was 71.1% in AR negative and 76.92% in AR positive, p=0.48. Median progression free survival in patients received the second line chemotherapy was 6 months in AR positive and 4 months in AR negative, p=0.0045. Median overall survival in AR positive patients was statistically significantly higher (12 months versus 9 months, р=0.04). Conclusions. Impact of AR expression on progression free and overall survival was proved for mTNBC patients received the second line chemotherapy. Keywords: metastatic triple negative breast cancer, androgen receptor, chemotherapy, progression free survival, overall survival.

Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kátia Ramos Moreira Leite ◽  
Carlos Henrique Barrios ◽  
Antônio Carlos Buzaid ◽  
Débora Gagliato ◽  
Helenice Gobbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Median Overall Survival ◽  
Triple Negative ◽  
Breast Cancer Treatment ◽  
Main Text ◽  
Critical Questions ◽  
Online Panel ◽  
Active Interest

Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease that represents 10–20% of breast cancer cases. The prognosis for advanced TNBC is usually poor, with a median overall survival of approximately 18 months or less. Main text New targeted therapies such as anti-PD-L1 agents are emerging as an option to treat advanced TNBC. A panel of 6 national experts with an active interest in breast cancer convened online. Panel members had either clinical or pathology experience in breast cancer. The experts pre-defined critical questions in the management of PD-L1 in TNBC, and a literature review was performed for selected topics before the online meeting. Conclusion The experts led active discussions involving a multidisciplinary team comprising pathologists and clinical oncologists. The meeting served to discuss the most relevant issues. A total of 10 critical questions for PD-L1+ TNBC were debated and are presented in this review. This article discusses the current landscape for PD-L1 tests in TNBC in Brazil.

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

2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
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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