Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone
Abstract 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 tha...
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BMC
2025-03-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-025-01992-0 |
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| author | James N. Ingle Vera J. Suman Malvika H. Solanki Marie R. Passow Jordan D. Campbell Liewei Wang Matthew P. Goetz |
| author_facet | James N. Ingle Vera J. Suman Malvika H. Solanki Marie R. Passow Jordan D. Campbell Liewei Wang Matthew P. Goetz |
| author_sort | James N. Ingle |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3992a97b5aed4f48b6748c9adf6cbf9d |
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| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Breast Cancer Research |
| spelling | doaj-art-3992a97b5aed4f48b6748c9adf6cbf9d2025-08-20T01:48:17ZengBMCBreast Cancer Research1465-542X2025-03-0127111210.1186/s13058-025-01992-0Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesteroneJames N. Ingle0Vera J. Suman1Malvika H. Solanki2Marie R. Passow3Jordan D. Campbell4Liewei Wang5Matthew P. Goetz6Division of Medical Oncology, Department of Oncology, Mayo ClinicDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicCytopathology Laboratory, Mayo ClinicDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo ClinicDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo ClinicDivision of Medical Oncology, Department of Oncology, Mayo ClinicAbstract 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.https://doi.org/10.1186/s13058-025-01992-0Androgen receptorEstrogen receptorTamoxifenFluoxymesterone |
| spellingShingle | James N. Ingle Vera J. Suman Malvika H. Solanki Marie R. Passow Jordan D. Campbell Liewei Wang Matthew P. Goetz Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone Breast Cancer Research Androgen receptor Estrogen receptor Tamoxifen Fluoxymesterone |
| title | Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone |
| title_full | Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone |
| title_fullStr | Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone |
| title_full_unstemmed | Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone |
| title_short | Evaluation of the androgen receptor in patients with ERα-positive early breast cancer treated with adjuvant tamoxifen ± fluoxymesterone |
| title_sort | evaluation of the androgen receptor in patients with erα positive early breast cancer treated with adjuvant tamoxifen fluoxymesterone |
| topic | Androgen receptor Estrogen receptor Tamoxifen Fluoxymesterone |
| url | https://doi.org/10.1186/s13058-025-01992-0 |
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