Evaluation Of The Prognostic Significance Of Androgen Receptor (Ar) Expression In Relation To Er Expression In Breast Cancer (Bc)

Abstract Background: AR is expressed in 60–80% of invasive BC. Emerging data suggest that AR expression may have a prognostic role in BC irrespective of ER and that the androgen-signaling pathway may be involved in BC pathogenesis. We previously identified an AR-dependent subset of ER/PR(−) BC and reported clinical benefit from AR-inhibition (Gucalp, ASCO 2012). We now describe the prevalence, clinicopathologic characteristics, and survival outcomes of AR(+) BC in relation to expression of ER in a single-institution retrospective cohort. Methods: We identified 590 patients (pts) with resectable BC (tumor >1cm) who had surgery at MSKCC from 1992–1996. IRB approval was obtained. Tissue microarray (TMA) construction/scoring has been described (Kalinsky CCR 2009). TMAs were stained, scanned and digitally scored (Aperio ScanScope XT) for nuclear steroid receptors (ER, AR), HER2, p53, and MIB1 (Ki67). Using digital quantification of tumor cell nuclear staining, pts were categorized into the following 7 groups: ER dominant (ERD, both ER and AR >10% with ER>AR by >5%), ER only (ER>10%, AR <10%), ER=AR (both >10%, <5% difference), AR dominant (ARD, both >10%, AR>ER by >5%), AR only (AR>10%, ER<10%), hormone receptor negative (HRN, both <10%) and unknown. Due to small pt numbers, ER=AR and ARD data were combined as were AR only and HRN. Associations between IHC expression and clinicopathologic features were assessed using the Chi-square/t-test. The Kaplan-Meier method, Cox proportional hazards models, and log-rank test were used to evaluate the association of IHC expression category on disease-free survival (DFS), distant (d)-DFS, and overall survival (OS). Results: 528 pts had adequate tumor cores for image analysis/quantification of AR; 302 (57%) tested AR(+). Median followup 12.8 years (yr). A significant difference in DFS (P = .0145), d-DFS (P = .006) and OS (P = .0485) was observed among the following groups: ERD, ER only, ER=AR/ARD and HRN/AR only, with a more favorable outcome associated with ERD (Table 1). In ER+ BC, ER=AR and ARD are associated with a high frequency of tumor MIB1, p53 and HER2 over-expression (Table 2). Conclusions: The degree of AR expression relative to ER may be prognostic as survival appears attenuated when AR is the more highly expressed steroid transcription factor. Other poor prognostic factors, including p53, HER2 and higher proliferation indices associate with this finding. The biology associated with AR dominance in ER+ BC needs further study. The inferior clinical outcome of the ER only category is in agreement with recent reports. Further analysis of PIK3CA mutational status and PI3K signaling pathway activation in relation to AR is ongoing. Supported in part by Geoffrey Beene Cancer Research Center at MSKCC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-01.