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Updated: Mar 30, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Androgen receptor status is highly conserved during tumor progression of breast cancer
André Grogg1, Mafalda Trippel2, Katrin Pfaltz3
1Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland. Andre.grogg@students.unibe.ch.
Background:
With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences.
Methods:
AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined.
Results:
AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17).
Conclusions:
Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.
Insights
Androgen receptor (AR) positivity is high in primary and metastatic breast cancer (BC), including triple-negative BC (TNBC). AR status is generally stable during tumor progression, supporting AR-targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) targeted therapies are emerging for breast cancer (BC), particularly triple-negative BC (TNBC).
- AR status is typically assessed in primary tumors, but its stability during tumor progression is poorly understood.
- Investigating AR status discrepancies between primary BC and metastatic sites is crucial for treatment strategies.
Purpose of the Study:
- To determine the prevalence of AR positivity in primary BC, metastases, and recurrences.
- To investigate the concordance of AR status between primary tumors and their corresponding metastatic lesions.
- To evaluate AR status in triple-negative breast cancer (TNBC) and its changes during tumor progression.
Main Methods:
- AR status was assessed in 356 primary BCs, 135 metastases, and 12 recurrences using immunohistochemistry on a next-generation Tissue Microarray (ngTMA).
- AR positivity was defined as any nuclear staining in ≥1% of tumor cells.
- Concordance rates of AR expression between primary tumors and matched metastases/recurrences were analyzed.
Main Results:
- AR positivity was high: 87% in primary tumors, 86.1% in metastases, and 66.7% in recurrences.
- AR positivity was observed in 11.4% of TNBC cases.
- Discrepancies in AR status between primary BC and lymph node metastases occurred in 4.3% of cases, with no changes noted in distant metastases or recurrences.
Conclusions:
- The majority of primary and metastatic breast cancers exhibit AR positivity, including a notable proportion of TNBCs.
- AR status remains largely consistent throughout tumor progression, with only minor changes observed.
- These findings support the potential efficacy of AR-targeted therapies for a broad range of BC patients and suggest re-testing AR status in specific cases.
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