Abstract PO1-13-06: Androgen Receptor Isoform V7 (AR-V7): A Promising Biomarker for Prognosticating Breast Cancer Aggressiveness

Abstract Androgen Receptor (AR) is an emerging endocrine therapy target in Breast Cancer (BrCa) with up to 80% expression in clinical cases. AR-V7 is a constitutively activated splice variant of AR having a truncated ligand-binding domain (LBD). This confers ligand-independent transcriptional activity to AR-V7 and makes it susceptible to nonsteroidal antiandrogens such as Bicalutamide or Enzalutamide which target the LBD of AR. Higher levels of AR-V7 in metastatic prostate cancer leads to therapeutic resistance and enhanced metastasis. We assessed AR-full length (AR-FL) and AR-V7 expression in BrCa cell lines of different molecular subtypes. This was extended for a clinical correlation of AR-FL and AR-V7 in validated treatment naïve BrCa patients undergoing surgical intervention at a tertiary care hospital in India. Transcriptomic and proteomic analysis was performed using qRT-PCR and Western Blotting. Immunocytochemistry and immunohistochemistry were used to examine protein expression and localisation in cells and tissues. AR-FL and AR-V7 were variably expressed in cell lines which got elevated with Dihydrotestosterone (DHT) treatment. Cell lines stimulated with Bicalutamide or Enzalutamide showed significant downregulation in AR-FL expression. From a cohort of 82 clinical cases, more than 50% originated from the urban setting, post-menopausal stage, and in the age groups of 61 to 70 years. ER, PR, HER2, and AR were positive in 65%, 55%, 24%, and 67% respectively. We were able to correlate aggressive clinical traits and higher pathological grades with increased expression of AR-V7 in the AR-positive BrCa fraction. This was consistent with the cell line-based preclinical research. This study affiliates AR-V7 as an important prognostic biomarker for predicting breast cancer aggressiveness. It can serve as a screening marker of poor clinical outcomes and aid in appropriate therapeutic intervention. These outcomes, however, seek extensive prospective validation. Citation Format: Tryambak Pratap Srivastava, Joyeeta Talukdar, Rohit Kumar Verma, Subhradip Karmakar. Androgen Receptor Isoform V7 (AR-V7): A Promising Biomarker for Prognosticating Breast Cancer Aggressiveness abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-06.