Abstract P5-02-08: Androgen receptor pathway activity and the ratio between androgen and estrogen receptor pathway activity in breast cancer subtypes

Background: Androgen receptor (AR) immunohistochemistry staining in breast cancer has revealed frequent AR expression in all breast cancer subtypes. Activity of the AR signaling pathway can be either tumor suppressive or tumor promoting, depending on tumor context (Pharmacol Ther., In press, https://doi.org/10.1016/j.pharmthera.2019.05.005). For this reason, in an individual patient, AR phenotypic activity needs to be defined in order to choose the proper AR targeted therapy. The AR/ER protein ratio has been suggested as a biomarker to define this AR function and enable the appropriate therapy choice, i.e. androgen therapy in case of a low AR/ER protein expression ratio, and anti-androgen therapy in case of a high ratio. However, AR and ER expression are not necessarily associated with an active signaling pathway. Therefore we investigated the ratio between functional AR and ER pathway activities as this may have an advantage in guiding therapy choice. Methods: AR and ER pathway activity and AR/ER pathway activity ratio were determined on public Affymetrix HG-U133 Plus 2.0 gene expression microarray data of clinical breast cancer studies (available in the GEO database: GSE12276, GSE21653, GSE20685, GSE42568, GSE6532, GSE9195, GSE45827, GSE7307, GSE10780, GSE17907, GSE21422, GSE5764, GSE31192, GSE54002 and Array Express: E-MTAB-365; total n=2090). For this, we used previously described tests that enable quantification of functional pathway activity, based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the ER and AR transcription factor (Cancer Res., 2014, vol. 74, no. 11, pp. 2936-2945; Sci Rep., 2019, vol. 9, no. 1, p. 1603). Intrinsic subtyping of all samples has been done using the same methodology as described elsewhere (Am J Pathol, 2018, vol. 188, no. 9, pp 1956-1972).Results: AR pathway activity was increased in all breast cancer subtypes compared to normal breast tissue (p Citation Format: Anja van de Stolpe, Yvonne Wesseling-Rozendaal, Marcia Alves de Inda, Henk van Ooijen, Wim Verhaegh. Androgen receptor pathway activity and the ratio between androgen and estrogen receptor pathway activity in breast cancer subtypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-08.