Abstract P6-08-47: Androgen receptor expression in pre-menopausal early breast cancer patients treated with endocrine therapy within the ABCSG-12 trial - a single center pilot analysis
Authors: Rinnerthaler Gabriel , Knopp Anna M , Hauser-Kronberger Cornelia , Gampenrieder Simon P , Morre Patrick , Mlineritsch Brigitte , Fesl Christian , Gnant Michael , Greil Richard 
Published: May 2015

Background: Estrogen-receptor (ER) positive breast cancer co-expresses androgen receptor (AR) in 75% to 95% of cases. The Austrian Breast & Colorectal Cancer Study Group (ABCSG) trial 12 compared anastrozole plus goserelin with tamoxifen plus goserelin in premenopausal patients with hormone receptor positive early breast cancer. In addition, patients were randomized to receive zoledronic acid or not. The aim of this analysis was to investigate the effect of AR expression on outcome in dependency of the treatment arm.

Patients and methods: AR expression was analyzed by immunohistochemistry using a mouse monoclonal antibody (Novocastra) in formalin-fixed paraffin-embedded specimens from 194 early breast cancer patients treated within the ABCSG 12 trial at our institution. As there is no generally accepted cut-off level defining AR positivity, we used two definitions for this analysis: A) positive staining of ≥ 10% of tumor cells B) an immune reactive score (IRS; intensity of staining X percentage of stained cells) ≥ 3 according to the Remmele score used for ER/PR evaluation.

Results: A total of 194 patients were included in this analysis. In tissue samples collected before 2001 AR staining was very weak, interpreted as a loss of antigenicity due to archival time and conditions. Therefore, 40 patients with tissue samples achieved earlier than 2001 were excluded from further analysis. Seventy-nine percent (122 of 154) and 63% (97 of 154) of tumors were AR positive by definition A and B, respectively. All except one of the AR positive tumors according to definition B, were also positive according to definition A.

Disease free survival (DFS) and overall survival (OS) data N (%)DFSOSDefinition A (≥ 10%)   AR positive122 (79)HR 0.61 (0.21-1.72) P=0.3428HR 0.17 (0.03-0.99) P=0.025AR negative32 (21)  Definition B (IRS ≥ 3)   AR positive97 (63)HR 0.88 (0.33-2.35) P=0.7994HR 0.39 (0.07-2.34) P=0.2846AR negative57 (37)  

DFS and OS did not differ between both endocrine treatment arms in a Cox regression model tested for interaction between AR expression and endocrine treatment.

Conclusion: In this pilot study patients with AR positive disease had a numerically better DFS and OS compared to AR negative patients, but only prolongation of OS in patients with ≥ 10% AR positive tumor cells was statistically significant. AR expression did not influence outcome between tamoxifen and anastrozole treated patients, but based on the small number of events, this results have to be interpreted with caution. This data will be confirmed in a larger proportion of patients treated within the ABCSG-12 trial.

Citation Format: Gabriel Rinnerthaler, Anna M Knopp, Cornelia Hauser-Kronberger, Simon P Gampenrieder, Patrick Morre, Brigitte Mlineritsch, Christian Fesl, Michael Gnant, Richard Greil. Androgen receptor expression in pre-menopausal early breast cancer patients treated with endocrine therapy within the ABCSG-12 trial - a single center pilot analysis [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 P6-08-47.