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AR Signaling in Breast Cancer

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Department of Medicine, Division of Hematology and Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA


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Academic Editor: Emmanuel S. Antonarakis

Abstract Androgen receptor AR, a member of the steroid hormone receptor family status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor ER positive breast cancer, and to a lesser degree, human epidermal growth factor 2 HER2 amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer TNBC, which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor LAR subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response pCR rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies. View Full-Text

Keywords: AR signaling; AR-PARP interplay; AR-BET interplay; breast cancer AR signaling; AR-PARP interplay; AR-BET interplay; breast cancer

Autor: Bilal Rahim and Ruth O’Regan *



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