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

Abstract

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.

Figures

Fig. 1

Examples of discrepant cases. a-f: TMA punches of matched primary BCs and matched lymph node metastases stained for the androgen receptor (AR) (100x magnification). a-b: patient ID 348; c-d: patient ID 47, e-f: patient ID 356. a Primary no special type (NST) BC with a negative androgen receptor (AR) status (<1 % positive tumor cells) and matched lymph node metastasis (b) with a positive, nuclear brown AR staining (1 % positive tumor cells). c Positive primary NST BC (5 % positive tumor cells) with some cytoplasmatic background and matched lymph node metastasis (d) with a negative AR status. The black arrow is pointing to the metastatic cells. On the bottom of the arrow some crush artifacts are visible. e Ductulo-lobular, primary BC with a positive and a negative (inlet) tumor component for AR. The matched lymph node metastasis (f) shows a negative AR status and some cytoplasmatic background