Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone

Sep 23, 2026

Uploaded by Miles

Background: Evaluate whether androgen receptor (AR) expression level affects outcomes in women with estrogen receptor alpha (ERα)-positive breast cancer, and validate preclinical evidence that AR-agonists benefit ER-positive tumors with high AR. Methods: Tissue microarrays from tamoxifen alone or tamoxifen plus fluoxymesterone arms were stained for ER and AR; outcomes were assessed across deciles and relapse-free survival (RFS) as primary endpoint. Results: Among assessable patients, enriched ER/AR patterns differed by arm; AR-enriched cases showed a significant RFS advantage for Tam+Flu. Conclusions: AR-agonists may be valuable in AR-enriched, ER-enriched disease and merit future trials.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Clinical relevance of AR in ER-positive breast cancer

Evidence from prior studies and AR/ER ratio

Preclinical rationale for AR-agonists

Ingle et al. Breast Cancer Research (2025) 27:40 [https://doi.org/10.1186/s13058-025-01992-0](https://doi.org/10.1186/s13058-025-01992-0) Breast Cancer Research RESEARCH Open Access Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone James N. Ingle 1* , Vera J. Suman2, Malvika H. Solanki3, Marie R. Passow4, Jordan D. Campbell2, Liewei Wang5 and Matthew P. Goetz 1 Abstract Background Our goal was to evaluate the impact of level of androgen receptor (AR) expression on outcomesin women with estrogen receptor α (ER) positive breast cancer. We sought to corroborate our preclinical findings that AR-agonists were efficacious in patients with ER-positive tumors that also expressed high levels of AR. Methods Tissue microarrays (TMAs) were prepared from primary tumor blocks from patients entered on a prospective randomized adjuvant trial of tamoxifen (Tam) alone or combined with fluoxymesterone (Flu), an AR-agonist,(NCCTG 89-30-52) . TMAs were stained for ER and AR and expression examined in decile increments (0–100%) of positive invasive tumor nuclei. The primary endpoint was relapse-free survival (RFS) . Results 301 (59%) of the 514 patients had sufficient tissue to determine ER and AR expression, where nuclear staining of > 70% was considered “enriched” and nuclear staining of ≤ 70% was considered “poor/moderate”. Eleven (4%) of these patients had poor/moderate ER staining and were excluded from these analyses. The proportion ofthe ERenriched tumors that also had AR-enriched expression levels was 56. 3% in the Tam arm and 51. 8% in the Tam + Flu arm. Within the AR-enriched patients, the cumulative incidence of RFS events showed an advantage forTam + Flu over Tam alone that reached significance (Gray’s test p = 0 . 0472) . Conclusions Our findings suggest that an AR-agonist may be of value in AR-enriched, ER-enriched breast cancersand should be studied in future trials because of the availability of new, more tolerable AR-agonists. Keywords Androgen receptor, Estrogen receptor, Tamoxifen, Fluoxymesterone *Correspondence: James N. Ingle [ingle.james@mayo.edu](ingle.james@mayo.edu) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Ingle et al. Breast Cancer Research (2025) 27:40 Introduction Estrogen receptor α (ER) is expressed in the majority of breast cancers in women and the vast majority of ER-positive breast cancers also express the androgen receptor (AR), e.g., 74.8% in review by Vera-Badillo [1], 85.9% in the Nurses’Health Study[2], but the AR is not routinely determined in clinical practice. This is despite numerous studies showing expression of AR was associated with improved outcomes [1–5] in early breast cancer. Of note, these studies defined AR positivity in

FAQs

What was the study’s primary goal regarding androgen receptor expression?

To evaluate how the level of androgen receptor (AR) expression influences outcomes in women with ERα-positive early breast cancer and to support preclinical findings that AR-agonists work best in tumors with high AR.

How were AR and ER expression levels measured in the study?

Tissue microarrays were stained for ER and AR, and expression was assessed in decile increments (0–100%) of positive invasive tumor nuclei.

What did the results show for relapse-free survival in AR-enriched patients?

In AR-enriched patients, Tamoxifen plus fluoxymesterone showed a cumulative incidence advantage for RFS over tamoxifen alone, reaching statistical significance (Gray’s test p = 0.0472).

What conclusion did the authors draw about future treatment development?

An AR-agonist may be valuable for AR-enriched, ER-enriched breast cancers, and should be tested in future trials using newer, more tolerable AR-agonists.

Sep 23, 2026

Uploaded by Miles