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Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival

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Abstract

Introduction

Breast cancer in older women tends to have more favourable biology, compared to younger women. Androgen receptor (AR) is significant for breast tumour carcinogenesis; however, the role of AR in older women has not been fully explored.

Methods

Surgical specimens were obtained from an existing series of 1758 older women (≥ 70 years) with primary breast cancer, treated in a single institution with long-term (≥ 37 years) follow-up. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and a panel of 24 biomarkers was measured by immunohistochemistry (IHC) in these TMAs. AR positivity was assessed by IHC and defined as H-score ≥ 40. The relationship between AR in this cohort was compared to an equivalent group of younger women (< 70 years, n = 1708); the panel of 24 biomarkers and breast cancer specific survival (BCSS) in the older cohort.

Results

AR was assessed in 509 samples. Overall, 59% of the older women cohort had positive expression of AR, compared to 63% in the younger cohort. AR positivity (regardless of age) was associated with smaller size of tumour, lower grade of tumour, lower tubule formation, lower nuclear polymorphism and lower mitotic frequency. AR positivity was associated with positive expression of oestrogen receptor (ER), progesterone receptor (PR), breast cancer gene 1 (BRCA1), cytokeratin (CK) 7/8, CK18, CK19, B cell lymphoma (Bcl)2 and Mucin 1 (Muc1) expression. Conversely, AR-positive expression was associated with negative expression of human epidermal growth factor receptor 2 (HER2), Ki-67, CK5, CK17, epidermal growth factor receptor (EGFR), and CD44 expression. Older women with AR-positive tumours had better BCSS compared to AR-negative tumours (p = 0.009).

Conclusions

There was no difference in AR expression between older and younger women with breast cancer. AR has prognostic potential in terms of BCSS. Further work is needed to investigate AR as a therapeutic target.

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Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article.

Author Contributions

Conceptulisation—Kwok-Leung Cheung, Andrew Green, Jamal Abdi. Methodology—Kwok-Leung Cheung, Andrew Green, Jamal Abdi. Formal analysis and investigation—Jamal Abdi. Writing—orginal draft preparation—Jamal Abdi, Jahnavi Kalvala. Writing—review and editing—Jahnavi Kalvala, Ruth Parks. Supervision—Ruth Parks, Andrew Green, Kwok-Leung Cheung.

Disclosures

Jahnavi Kalvala, Ruth Parks, Jamal Abdi, Andrew Green, and Kwok-Leung Cheung have nothing to disclose.

Compliance with Ethics Guidelines

The research Nottingham Research Ethics Committee 2 approved the study under ethical approval number C2020313. Individual patient consent was not required as determined by the review board.

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

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Authors and Affiliations

  1. Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK

    Jahnavi Kalvala, Ruth M. Parks, Jamal Abdi, Andrew R. Green & Kwok-Leung Cheung

  2. Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby, DE22 3DT, UK

    Kwok-Leung Cheung

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Kalvala, J., Parks, R.M., Abdi, J. et al. Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival. Adv Ther 40, 2820–2835 (2023). https://doi.org/10.1007/s12325-023-02504-2

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