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Introduction: Triple Negative Breast Cancer (TNBC) is a dreadful molecular subtype due to its aggressiveness and heterogeneity. The presence of Androgen Receptor (AR) signaling plays a pivotal role in tumor progression and metastasis. The anti-androgens are exhibiting better responses in treating prostate cancers. Luminal-Androgen Receptor (LAR+TNBC) is one of the TNBC subtypes in which AR is present. In this study, it has been envisaged that targeting AR with AR antagonists for the treatment of TNBCs would be a better therapeutic regimen. We also identified the incidence of Androgen Receptor positivity in TNBC patients of Western India. Methods: The effectiveness of AR antagonists (Bicalutamide & Enzalutamide) were tested using in-vitro studies. Assessment of cell viability was determined by MTT assay in Human Breast cancer cell lines MDA-MB-453 (LAR+TNBC), MDA-MB-231 (TNBC), and MCF-7 (ER+PR+). The genotypic and phenotypic expressions of AR were analyzed via qRT-PCR and western blotting, respectively. Fifty TNBC patients were enrolled at The Gujarat Cancer and Research Institute, Ahmedabad, and AR expression was determined by Immunohistochemistry. Results: Based on the cell IC-50 values, both AR antagonists showed significant response in both TNBC cell lines but not significant in MCF-7. Moreover, Enzalutamide showed a better response in both TNBC cell lines than Bicalutamide. In the case of the study in TNBC patients, AR positivity was 18%, and, the incidence was correlated with clinicopathological prognosticators and disease status. Conclusion: The incidence of AR positivity in TNBC patients is about 20% and the preliminary in vitro studies showed that both AR antagonists can be explored as a therapeutic regimen for TNBCs. However, further, the role of AR signaling and its underlying mechanisms will be explored for a better understanding of AR as an independent biomarker for TNBCs. [ABSTRACT FROM AUTHOR]

• Hereditary Breast cancer (BC) and ovarian cancer (OC) pertain to higher mortality and need an early diagnosis. • The whole-exome sequencing (WES), is the powerful techniques of Next Generation Sequencing (NGS) delineated gene variants associated with the HBOC in the west Indian population. • The WES examination provided novel and prevalent variants in the population which could be further studied. Breast and ovarian cancers are the most common cancer types in females worldwide and in India. Patients with these cancers require an early diagnosis which is essential for better prognosis, treatment and improved patient survival. Recently, the utilization of next-generation sequencing (NGS)-based screening has accelerated molecular diagnosis of various cancers. In the present study, we performed whole-exome sequencing (WES) of 30 patients who had a first or second-degree relative with breast or ovarian cancer and are tested negative for BRCA1/2 or other high and moderate-risk genes reported for HBOC. WES data from patients were analyzed and variants were called using bcftools. Functional annotation of variants and variant prioritization was performed by Exomiser. The clinical significance of variants was determined as per ACMG classification using Varsome tool. The functional analysis of genes was determined by STRING analysis and disease association was determined by open target tool. We found novel variants and gene candidates having significant association with HBOC conditions. The genes identified by exomiser (phenotype score > 0.75) are associated with various biological processes such as DNA integrity maintenance, transcription regulation, cell cycle regulation, and apoptosis. Our findings provide novel and prevalent gene variants associated with the HBOC condition in the West Indian population which could be further studied for early diagnosis and better prognosis of HBOC. [ABSTRACT FROM AUTHOR]