Androgen receptor in breast cancer: A wolf in sheep’s clothing? A lesson from prostate cancer.

Salvi, Samanta; Bonafè, Massimiliano; Bravaccini, Sara

doi:10.1016/j.semcancer.2019.04.002

Cited by 39 publications

(43 citation statements)

References 52 publications

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“…Up till now, there is no clinical guideline concerning the methods to test AR positivity. Immunohistochemistry (IHC) is the cheapest method and is widely used in the definition of AR positivity in BC ( 12 ). The optimal cut-off point has not yet been identified; the discrepancy rate of AR expression between primary BC and metastatic tissue, and the influence of multiple antibodies on AR status, make it hard to explain the role of AR or select patients for AR-targeted therapy according to the expression data obtained by IHC ( 108 , 109 ).…”

Section: Discussionmentioning

confidence: 99%

“…Natural and synthetic androgens have been used as a treatment approach in BC with AR expression ( 12 , 66 , 67 ); however, they have been known to induce many side effects ( 68 ). The new selective-AR modulators (SARM), as AR agonists, can solve this problem ( 69 ).…”

Section: Ar-related Therapies In Bcmentioning

confidence: 99%

“…The AR-directed antagonists are mostly used in advanced BC, especially TNBC ( 12 ). Preclinical studies detected bicalutamide to inhibit proliferation and increase apoptosis in AR+/ER-negative BC cell lines, and even in the MSL TNBC BC cells, Hs578T and MDA-MB-231, which express relatively low levels of AR ( 9 , 78 ).…”

Section: Ar-related Therapies In Bcmentioning

confidence: 99%

“…Recently, the implication of AR in various stages of BC gathered significant attention. Although there have been several reviews discussing the physiology of AR, AR-related mechanisms, and AR-targeting treatments, its function appears to vary among the diverse BC subtypes, and its prognostic and predictive value in BC patients remains controversial ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Androgen Receptor in Breast Cancer: From Bench to Bedside

Chen

Yang

et al. 2020

Front. Endocrinol.

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Breast cancer (BC) is one of the most common malignancies and the leading cause of cancer-related mortality in women. Androgen receptor (AR) is frequently expressed in diverse BC subtypes. Accumulating evidence has revealed that AR might be a predictive or prognostic factor and a drug target in BC. AR expression and AR pathways differ in various BC subtypes, thereby resulting in controversial inferences on the predictive and prognostic value of AR. Herein, we summarized the roles of AR in different BC subtypes and AR-targeting therapies based on preclinical and clinical studies. Moreover, we highlighted the possible efficacy of a combination therapy via exploiting the AR-related mechanisms and the research on therapeutic resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Ar-related Therapies In Bcmentioning

confidence: 99%

Section: Ar-related Therapies In Bcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Androgen Receptor in Breast Cancer: From Bench to Bedside

Chen

Yang

et al. 2020

Front. Endocrinol.

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“…22,23 Additionally, AR targeted treatments in both preclinical and clinical findings for breast cancer are in development and have shown promising preliminary efficacy. 24 The gene expression studies identified that CLDN8 is driven by AR in the luminal androgen receptor (LAR) tumors, which is a subtype of TNBC. 25 It was reported that CLDN8 is an AR target gene and its transcriptional activation is up-regulated followed by DHT treatment in the breast cancer cells.…”

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confidence: 99%

<p>The Expression and Prognostic Significance of Claudin-8 and Androgen Receptor in Breast Cancer</p>

Zhang

Zheng

et al. 2020

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Purpose: Claudin-8 (CLDN8) has been identified as an androgen-regulated gene in prostate cancer. However, the role of CLDN8 has not been fully explored in breast cancer. We aimed to explore the expression of CLDN8 and androgen receptor (AR), determine the correlation between CLDN8 and AR, assess the prognostic value of CLDN8 and AR co-expression, and investigate the possible CLDN8 expression molecular mechanism in breast cancer. Materials and Methods: Twenty-eight pairs of fresh tumor tissues and adjacent noncancerous tissues were evaluated by Western blot for CLDN8. Then, 142 breast cancer samples were determined by immunohistochemistry for CLDN8 and AR. The association of clinicopathological features with CLDN8, AR and CLDN8, and AR co-expression was examined. The Cancer Genome Atlas (TCGA) was used to demonstrate the expression of CLDN8 and correlation between CLDN8 and AR. Kaplan-Meier survival analysis was performed to assess the prognostic impact of CLDN8 and AR co-expression. The mechanisms related to CLDN8 expression in breast cancer were explored by Gene Set Enrichment Analysis (GSEA). Results: CLDN8 was downregulated in breast cancer tissues and positively correlated with none lymph node metastasis (P=0.016), low histological grade (P=0.006), positive ER (P=0.014), positive PR (P=0.003), low Ki-67 index (P=0.017) and molecular subtypes (P=0.012). CLDN8 level was significantly associated with AR level (r=0.348; P<0.001). CLDN8 and AR coexpression was positively correlated with none lymph node metastasis (P=0.007), low histological grade (P=0.017), positive ER (P=0.019), positive PR (P=0.015) and low Ki-67 index group (P=0.038). CLDN8 and AR co-expression had a better clinical prognosis. Conclusion: The expression of CLDN8 is directly related to the expression of AR. CLDN8 and AR co-expression might be a potential prognostic evaluation factor for breast cancer patients.

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