TY - JOUR T1 - Molecular Analysis of Luminal Androgen Receptor Reveals Activated Pathways and Potential Therapeutic Targets in Breast Cancer JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 464 LP - 476 DO - 10.21873/cgp.20333 VL - 19 IS - 4 AU - STEFANIA STELLA AU - SILVIA RITA VITALE AU - MICHELE MASSIMINO AU - GIANMARCO MOTTA AU - CLAUDIO LONGHITANO AU - KATIA LANZAFAME AU - FEDERICA MARTORANA AU - CARMINE FAZZARI AU - GIADA MARIA VECCHIO AU - ELENA TIRRĂ’ AU - NICOLA INZERILLI AU - ROSARIA CARCIOTTO AU - LIVIA MANZELLA AU - MICHELE CARUSO AU - PAOLO VIGNERI Y1 - 2022/07/01 UR - http://cgp.iiarjournals.org/content/19/4/464.abstract N2 - Background/Aim: Triple-negative breast cancers represent 15% of all mammary malignancies and encompass several entities with different genomic characteristics. Among these, luminal androgen receptor (LAR) tumors express the androgen receptor (AR) and are characterized by a genomic profile which resembles luminal breast cancers. Moreover, LAR malignancies are usually enriched in PIK3CA, KMTC, CDH, NF1, and AKT1 alterations. Still, molecular features, clinical behavior and prognosis of this variant remain controversial, while identification of effective treatments represents an unmet medical need. Additionally, the predictive role of the AR is unclear. Materials and Methods: We performed an extensive next generation sequencing analysis using a commercially available panel in a cohort of patients with LAR breast cancer followed at two local Institutions. We next employed bioinformatic tools to identify signaling pathways involved in LAR pathogenesis and looked for potentially targetable alterations. Results: Eight patients were included in the study. In our cohort we found 26 known genetic alterations (KGAs) in 15 genes and 64 variants of unknown significance (VUS) in 59 genes. The most frequent KGAs were single nucleotide variants in PIK3CA, HER2, PTEN and TP53. Among VUS, CBFB, EP300, GRP124, MAP3K1, RANBP2 and TSC2 represented recurrently altered genes. We identified five signaling pathways (MAPK, PI3K/AKT, TP53, apoptosis and angiogenesis) involved in the pathogenesis of LAR breast cancer. Several alterations, including those in PIK3CA, ERBB2 and PI3K/AKT/mTOR signaling, were potentially targetable. Conclusion: Our findings confirm a role for PI3K/AKT/mTOR signaling in the pathogenesis of LAR breast cancers and indicate that targeting this pathway, along with ERBB2 mutations, may represent an additional therapeutic strategy which deserves further exploration in larger studies. ER -