Androgen receptor status is highly conserved during tumor progression of breast cancer.

Claudia Lädrach,Bodour Salhia,André Grogg,Katrin Pfaltz,Mafalda Trippel,Raoul A Droeser,Martin Zweifel,Coya Tapia,Nikola Cihoric

doi:10.1186/s12885-015-1897-2

Abstract

BackgroundWith 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.MethodsAR 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.ResultsAR 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).ConclusionsMost 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.

Highlights

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
AR status was informative in 99.2 % (353/356) of primary BCs, 90.4 % (122/135) of metastases and in 100 % (12/12) of the recurrences
In a recent study, which included a small series of triple negative BC (TNBC) with matched recurrences (n = 16) and lymph node metastases (n = 46), it was shown that AR discrepancies between primary tumors and metastasis did not occur [19]

Summary

Introduction

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. 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. In a Phase II clinical trial it was shown that patients with AR positive BC had a benefit from anti-androgenic therapy [7] indicating that targeting AR might be a therapeutic option. AR changes during tumor progression would have important clinical implications for patient selection of anti-AR therapy

Methods

Results

Discussion

Conclusion