Abstract

1027 Background: Basal-like breast cancer is a specific subtype of breast tumors with limited therapeutic options. Although treatment with the anti-PD-L1 antibody atezolizumab has recently shown clinical activity in this setting, not all patients do respond even expressing high levels of PD-L1. In the present article we explored the presence of mutations in breast cancer tumors with high expression of PD1 and PD-L1 with the aim to identify molecular correlates associated with outcome. Methods: We used RNA-seq and mutational data from 971 breast cancer patients using the TCGA dataset, to identify mutations in patients with high levels of PD1 and PD-L1. Data analysis was performed using DESeq R and MAFTools Bioconductor packages. Transcriptomic signatures from the identified mutations were associated with outcome using the Kapplan-Meyer Plotter tool. We correlated the identified transcripts with immune populations using TIMER online tool and correlation between genes with Cancertool online platform. Results: We identified co-occurrent mutations in RYR2 and AHNAK in 8% and 5% of basal like tumors, respectively, in patients with high levels of PD1 and PD-1. The transcriptomic signature of these mutations conferred good prognosis for relapse free survival (RFS) and overall survival (OS). CXCL9 for RYR2 and GBP5, C1QA, IL2RG, CSF2RB and IDO1 for AHNAK were the most relevant genes identified in these signatures. Expression of CXCL9, GBP5, IL2RG and IDO1 correlated with the presence of immune cell populations mainly dendritic cells. This signature, including CXCL9, GBP5, C1QA, IL2RG, CSF2RB and IDO1 classified patients with favorable RFS (HR 0.27 CI 0.2-0.30; p = 1.1e-16) and OS (HR 0.18 CI 0.09-0.34; p = 6.8e-9). This signature showed a stronger prediction capacity compared with already described immunologic signatures. Finally we identify that LAG3 was the only gene commonly present in both signatures and correlated positively with the expression of PD1 and PD-L1. Conclusions: We describe two novel mutations which transcriptomic signatures associated with favorable outcome in basal-like tumors that express elevated levels of PD1 and PD-L1. Future studies should be performed to confirm the role of these mutations and signatures in relation with clinical activity of PD1/PD-L1 inhibitors.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.