A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1)

Bonnefoi, Hervé; Grellety, Thomas; Trédan, Olivier; Saghatchian, Mahasti; Dalenc, Florence; Mailliez, Audrey; L’Haridon, Tifenn; Cottu, Paul; Abadie‐Lacourtoisie, Sophie; You, Benoît; Mousseau, M; Dauba, Jérôme; Piano, Francesco Del; Desmoulins, Isabelle; Coussy, Florence; Madranges, Nicolas; Grenier, Julien; Bidard, François-Clément; Proudhon, Charlotte; MacGrogan, Gaëtan; Orsini, C.; Pulido, Marina; Gonçalvès, Anthony

doi:10.1093/annonc/mdw067

Cited by 247 publications

(202 citation statements)

References 18 publications

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“…An example is the Luminal AR subtype, characterized by the expression of the androgen receptor; antiandrogens have recently demonstrated some activity and are being further evaluated, and where a potential predictive marker, the Predict AR assay, is also being tested [49, 50]. …”

Section: Triple Negative Abcmentioning

confidence: 99%

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Cardoso¹,

et al. 2017

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Section: Triple Negative Abcmentioning

confidence: 99%

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Cardoso¹,

et al. 2017

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“…Immunostained sections were scanned using a microscope (Aiovert 200, Carl Zeiss). According to previous researches [19, 20], a cut-off of 10% - those below this being classified as negative and those above being positive – was used in our assessment of AR and GPER expression. All the assessments were done in a blinded manner and determined independently by two senior pathologists.…”

Section: Methodsmentioning

confidence: 99%

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Shen

Yang

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: The targeted therapy for triple-negative breast cancer (TNBC) is still challenging due to poor understanding on its molecular etiology. The androgen receptor (AR) has recently emerged as a prognostic and treatment-predictive marker in breast cancer. However, the role of AR in TNBC remained elusive. Methods: Immunohistochemistry (IHC) was used to detect AR and G-protein coupled estrogen receptor (GPER) expression in tissue microarrays of 165 TNBC patients. Microarray analysis of mRNAs was performed to identify downstream regulators of AR. TNBC cells were cultured with dihydrotestosterone (DHT) alone or in combination with AR knockdown performed with AR shRNA. Cell viability and colony formation were assessed. Western blotting and qRT-PCR were used to examine protein and mRNA expression, respectively. The potential mechanism of AR-mediated GPER suppression was identified by Chromatin immunoprecipitation (ChIP) assay. AR and GPER expressions were also assessed in nude mouse xenografts by IHC. Results: IHC staining showed that the expression of AR was positively associated with tumor size, lymph node metastasis and high-grade tumor in TNBC patients. AR activation triggered by DHT suppressed GPER expression, to promote cell growth of TNBC. G-1, a GPER agonist, inhibited DHT-stimulated proliferation. Further experiments illustrated that AR suppressed GPER activation via binding directly to the promoter of GPER. Moreover, a negative correlation between AR and GPER was observed in MDA-MB-231 tumor cell xenografts and TNBC patient samples. Conclusions: The suppression of GPER via AR may be involved in the positive actions towards the TNBC progression, making it a promising therapeutic target for TNBC treatment.

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“…These inhibitors reduce the androgen production and the androgen levels. They are now being tested in phase 2 clinical trials (59, 60), alone or in combination with AR antagonists (61). …”

Section: Androgen Targeted Therapymentioning

confidence: 99%

The Androgen Receptor in Breast Cancer

et al. 2018

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Breast cancer (BC) is a hormone-related tumor. Despite the progress in BC therapy, this disease still remains the most common cancer amongst women around the world. This is likely due to the amazing BC heterogeneity. Accumulating evidence suggests a role for androgen signaling in BC. Nevertheless, a precise understanding of the mechanism of androgen action in this disease remains a challenging puzzle. Androgen receptor (AR) is often expressed in BC and several studies suggest that its role depends on the tumor microenvironment as well as the relative levels of circulating estrogens and androgens. However, the AR function in BC is still conflicting. Although AR expression is often associated with a favorable prognosis in EREstradiol Receptorα-positive (ERα +) BC, many findings suggest that, in some instances, high levels of AR can contribute to the therapy-resistance. Again, in ERα negative BC (ERα –), AR is mainly expressed in tumors with apocrine differentiation and a lower Nottingham grade. Moreover, AR stimulates cellular proliferation in triple negative breast cancer (ERα –, PgR –, and HER-2-Neu –). This finding is substantiated by the observation that high levels of circulating androgens are associated with an increased risk of developing BC in post-menopausal woman. Treatment of ERα- BC with AR antagonists, such as bicalutamide or enzalutamide, reduces, indeed, the tumor growth. In this review, we will analyze the putative role of AR in BC. Emerging therapies based on the use of new agonists or antagonists or inhibitors will be here discussed.

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A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1)

Cited by 247 publications

References 18 publications

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

The Androgen Receptor in Breast Cancer

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