Abstract P3-06-20: Druggable genomic landscape of primary and metastatic breast cancers

Abstract

Abstract Background: Several studies (e.g. The Pan-Cancer Atlas) have examined the druggable genomic landscape of breast cancers and other malignancies using The Cancer Genome Atlas (TCGA). However, TCGA is representative of newly-diagnosed, treatment-naïve breast cancers, whereas genomic profiling is typically used to inform therapy for metastatic and/or pre-treated breast cancers. Here, we characterize the druggable genomic landscape of breast cancers using AACR Genomics Evidence Neoplasia Information Exchange (GENIE), a multi-institutional pragmatic cancer genomics registry. Methods: We obtained mutation, copy-number amplification (CNA), and fusion data from GENIE, which contains de-identified genomic records from 4506 breast carcinoma and carcinoma-in-situ (CIS) tumors. We used Clinical Interpretation of Variants in Cancer (CIViC) to label the potential druggability of these mutations, CNAs, and fusions. Further, we plan to assess variations in the druggable genomic landscape of breast tumors as a function of tumor characteristics (e.g. histology, tumor mutation burden), patient characteristics (age, sex, ethnicity), and genomics assay characteristics (e.g. PCR vs. hybridization capture). Results: In GENIE, we identified 19932 mutations, 9334 copy number amplifications (CNA), and 987 fusions in 4506 breast tumors. CNAs suggesting potential druggability were relatively common (e.g. ERBB2 amplifications in 9.9% of tumors), whereas fusions suggesting potential druggability were relatively rare (e.g. NTRK fusions in 0.1% of tumors). Mutations suggesting potential druggability were identified in ERBB2 (3.5% of tumors) and mismatch repair genes [MLH1, MSH2, MSH3, MSH6, PMS1, PMS2] (3.7% of tumors). Conclusion: GENIE can be used to infer druggability across a cohort of breast tumors likely to be considered for approved systemic therapy at tertiary academic centers. This may inform use of genomic assays and/or design of clinical trials for patients with breast tumors. *The author would like to acknowledge the American Association for Cancer Research and its financial and material support in the development of the AACR Project GENIE registry, as well as members of the consortium for their commitment to data sharing. Interpretations are the responsibility of study authors. Citation Format: Sun SQ. Druggable genomic landscape of primary and metastatic breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-20.