Abstract P3-04-07: Androgen receptor expression in triple negative breast cancer
Authors: Gilmore Hannah , Varadan Vinay , Williams Nicole , Thompson Cheryl L , Kim Stephanie , Hsu Peter , Miskimen Kristy , Palkar Aditi , Vinayak Shaveta , Lindner Robert , Harris Lyndsay 
Published: May 2015

Background: Patients with androgen receptor (AR) positive triple-negative breast cancer (TNBC) may derive a significant benefit from anti-androgen therapy. While AR positivity is often defined by protein expression by immunohistochemistry (IHC), the benefit of anti-androgen therapy in patients who have the Luminal Androgen Receptor (LAR) molecular subtype as defined by genomic profiling is unclear. Our aim was to study the clinical, pathologic and molecular profiles of AR+ tumors by IHC in a diverse set of TNBC.

Methods: Tissue microarrays from two separate, well-annotated institutional cohorts (Case Western Reserve University, Yale University) of early-stage TNBC were evaluated for AR expression by IHC (clone SP107, Ventana Benchmark Ultra). AR positivity was defined as greater than or equal to 10% staining in tumor nuclei. AR expression was correlated with clinical and pathologic features such as age, race, grade, and stage within and between the two cohorts. Gene expression was analyzed with the DASL assay (Illumina) on RNA extracted from formalin-fixed paraffin-embedded material using the Ambion RecoverAll kit (Applied Biosystems AM1975). Pietenpol TNBC molecular subtypes were calculated using the online TNBC type tool. Co-expression of AR with other hormone-related proteins including gross cystic disease fluid protein-15 (GCDFP-15, clone EP1582Y, Ventana Benchmark Ultra) and GATA transcription factor 3 (GATA3, clone L50-823, Bondmax Leica) were also assessed.

Results: Overall, 22% of cases (n=192) were AR+ by IHC. There was no association between AR expression and age, race, grade or stage within or between the two cohorts. Gene expression data was available on 88 tumors with AR staining results and demonstrated that AR positivity by IHC was not exclusive for the TNBC LAR molecular subtype. Three of five (3/5) tumors that were classified and LAR were in fact AR+ by IHC. Tumors that were AR+ by IHC were also identified in the basal-like 2 (BL2), mesenchymal stem-like (MSL), immunomodulatory (IM), and unstable molecular TNBC categories with low frequency. Notably, of cases that were rejected as ER+ by gene expression profiling despite being clinically TNBC, three of five (3/5) were in fact AR+ by IHC. Examination of other hormone-related proteins in a subset of these patients revealed that AR expression was significantly associated with GCDFP-15 expression (p=0.0007) and was borderline significant for GATA3 expression (p=0.068).

Conclusions: AR protein expression levels by IHC were similar in two separate institutional archival cohorts of TNBC and did not correlate with age, race, grade or stage. Comparison of AR IHC data with genomic data suggests that the AR+ phenotype is not unique to LAR subtype of TNBC by gene expression profiling. AR protein expression may be seen in clinically TNBC patients who have a more luminal subtype as evidenced by co-expression of GCDFP-15 and GATA3. Our results suggest that AR staining by IHC may be necessary to capture all patients who may benefit from anti-androgen therapy.

Citation Format: Hannah Gilmore, Vinay Varadan, Nicole Williams, Cheryl L Thompson, Stephanie Kim, Peter Hsu, Kristy Miskimen, Aditi Palkar, Shaveta Vinayak, Robert Lindner, Lyndsay Harris. Androgen receptor expression in triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-07.