Abstract 2774: Androgen receptor is an independent prognostic marker of breast cancer in ethnically diverse women from Chicago
Authors: Mahmoud Abeer M. , Al-alem Umaima , Macias Virgilia , Kresovich Jacob K. , Kajdacsy-Balla Andre , Wiley Elizabeth L. , Rauscher Garth H. 
Published: August 2015

Androgen receptor (AR) has been demonstrated to be a prognostic marker in invasive breast cancer; higher expression levels of AR is associated with better prognosis among breast cancer patients. The goal of this analysis was to examine the extent to which AR was associated with specific breast cancer subtypes, and whether it could serve as an additional prognostic marker above and beyond breast cancer subtype, in an ethnically diverse sample of 287 patients (86 Non-Hispanic White, 84 Hispanic and 116 African American). Immunohistochemical analysis was performed on tissue microarrays constructed from invasive breast cancer samples obtained from the Breast Cancer Care in Chicago study. Tissue samples were tested for the expression of estrogen receptor (ER), progesterone receptor (PR), HER2. From these results, breast cancers were classified as Luminal A (ER+/PR+/HER2-), Luminal B (ER+/PR+/HER2+), HER2 enriched (ER-/PR-/HER2+), and triple negative (TN) (ER-/PR-/HER2-). Tumor tissues were also analyzed for the expression of other proliferative and apopototic markers (i.e. Ki67, P53 and bcl2) as well as BRCA1 protein expression. AR expression was evaluated based on the percentage of positive tumor cells and staining intensity using the H-score. The H score is a product of the percentage of cells (0-100%) in each intensity category (0, 1+, 2+ and 3+). The final score is on a continuous scale between 0 and 300. AR expression was then classified as low (&lt;60%) or high (≥60%) using the mean of the AR score as a cutoff. Among the 287 breast cancer cases, 59% were expressing low levels of AR while 41% were expressing high AR. The percentage of tumor samples with high AR expression was much higher for luminal A (52%) than for luminal B, HER2, and TN subtypes (43, 29, and 9%, respectively(P&lt;0.0001). High AR expression significantly correlated with early stage (P = 0.01), lower nuclear grade (P&lt;0.0001), ER and PR positivity (P&lt;0.0001), bcl2 positivity(P&lt;0.0001), higher levels of BRCA1 expression (P&lt;0.0001), lower Ki67 index (P&lt;0.0001), and lower P53 expression (P&lt;0.0001). A hormone receptor expression score (HRES) with a high internal reliability (Cronbach's alpha = 0.7035) was created based on standardized variables for ER, PR and AR expression. Using an ordinal logistic regression model, the HRES was a highly significant predictor of tumor grade (P&lt;0.0001). In conclusion, in this multi-ethnic sample of breast cancer patients, we found that AR was a significant independent predictor of less aggressive, lower grade disease, even after accounting for molecular subtype. AR might serve as a useful additional marker for the classification of breast cancer into molecular subtypes.

Citation Format: Abeer M. Mahmoud, Umaima Al-alem, Virgilia Macias, Jacob K. Kresovich, Andre Kajdacsy-Balla, Elizabeth L. Wiley, Garth H. Rauscher. Androgen receptor is an independent prognostic marker of breast cancer in ethnically diverse women from Chicago. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2774. doi:10.1158/1538-7445.AM2015-2774