Journal Article

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

Solanki, Malvika H., Passow, Marie R., Goetz, Matthew P., Campbell, Jordan D., Wang, Liewei, Suman, Vera J., Ingle, James N.

2025

Overview

Background Our goal was to evaluate the impact of level of androgen receptor (AR) expression on outcomes in 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 of the ER-enriched 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 for Tam + 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 cancers and should be studied in future trials because of the availability of new, more tolerable AR-agonists.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adult / Aged / Agonists / Androgen receptor / Androgen receptors / Androgens / Antineoplastic Agents, Hormonal - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer / Cancer Research / Cell growth / Chemotherapy, Adjuvant / Clinical trials / Endocrine therapy / Estrogen receptor / Estrogen Receptor alpha - genetics / Estrogen Receptor alpha - metabolism / Estrogen receptors / Female / Fluoxymesterone / Humans / Influenza / Laboratories / Medical diagnosis / Medical prognosis / Middle Aged / Oncology / Patients / Receptors, Androgen - genetics / Receptors, Androgen - metabolism / Surgical Oncology / Tamoxifen / Tamoxifen - administration & dosage / Tamoxifen - therapeutic use / Tissue Array Analysis / Treatment Outcome / Tumors / Womens health