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AR pathway activity correlates with AR expression in a HER2-dependent manner and serves as a better prognostic factor in breast cancer

  • Dingxie LiuEmail author
Original paper
  • 39 Downloads

Abstract

Background

Androgen receptor (AR) antagonists are currently tested in multiple clinical trials for different breast cancer (BC) subtypes, which emphasizes the need for clarifying the role of AR in this type of cancer. Previous studies showed that AR expression was associated with a favorable prognosis in ER-positive BC. However, the true biological effect of AR signaling in BC is not clear.

Methods

An AR pathway signature was generated to compute AR pathway activity in BCs (n = 6439) from 46 microarray datasets. Associations of AR pathway activity and AR expression with BC prognosis were compared by survival analysis.

Results

AR pathway activity showed moderate positive and negative correlations with AR expression in HER2-positive and HER2-negative BCs, respectively. AR pathway activity increased while AR expression decreased in ER-negative BCs. Like ER and progesterone receptor (PR) expression, AR expression was also negatively associated with tumor grade, neoadjuvant response, and recurrence risk in BC. By contrast, AR pathway activity was positively, and more significantly, associated with these clinical features. Moreover, the AR pathway, but not AR expression, was significantly associated with recurrence risk in BC patients treated with endocrine therapy. These data suggest that, although AR expression probably reflects well-differentiated states of BC and is thus associated with favorable prognosis in BC, the biological effects of AR signaling confers worse outcomes in BC.

Conclusions

Our findings encourage the continued evaluation of AR antagonists for BC treatment and support that AR pathway activity serves as a better prognostic factor than AR expression in BC.

Keywords

Breast cancer Androgen receptor pathway Estrogen receptor HER2 Gene signature Endocrine therapy Prognosis prediction 

Notes

Acknowledgments

The results here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. We are also very grateful to the investigators who contributed the breast cancer microarray datasets that we used in this study.

Compliance with ethical standards

Disclosure of conflict of interest

Bluewater Biotech LLC has filed a provisional patent for the results in this paper. Dingxie Liu has an equity interest in Bluewater Biotech LLC.

Supplementary material

13402_2019_492_MOESM1_ESM.pdf (23.6 mb)
ESM 1 (PDF 24185 kb)
13402_2019_492_MOESM2_ESM.xlsx (18 kb)
ESM 2 (XLSX 17 kb)

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Copyright information

© International Society for Cellular Oncology 2020

Authors and Affiliations

  1. 1.Bluewater Biotech LLCNew ProvidenceUSA
  2. 2.Division of Endocrinology, Diabetes & Metabolism, Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA

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