Abstract P3-07-01: Towards a therapeutically relevant subtyping scheme for triple-negative breast cancer (TNBC), profiling results from A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival (ARTEMIS)

Triple-negative breast cancer is a highly diverse group of cancers, with poor prognosis, and currently, there are no targeted drugs available in the clinic. In TNBC around 50% percent of the patients respond to chemotherapy, while, the other 50% percent relapse with poor prognosis. There is a need to understand better the targetable mechanisms driving TNBC via integrative analysis of gene-expression, copy-number, and mutational data. Samples from 220 triple-negative breast cancer (TNBC) pts treated with NACT were prioritized for transcriptomic and genomic profiling. Non-negative matrix factorization was used on array-based profiling to identify six robust (ARTEMIS) subtypes. Comparing ARTEMIS subtypes with Vanderbilt subtypes, revealed significant overlap with 4/6 clusters while identifying two new clusters. Logistic regression on ssGSEA scores vs. subtypes revealed several pathways, selectively enriched specific subtypes. CL1/IM (Immune subtype), was enriched in INFg and INFa, while CL2 (MYC/mTOR), showed enrichment of several proliferation-related pathways. In addition, LAR and M (Mesenchymal) pts formed overlapping clusters, using either method. Two new subtypes did not associate significantly with any of the previous subtypes. The majority of the tumors from the Vanderbilt BL2 and MSL were reclassified into a CL5 (ANGIO) cluster, which was enriched in angiogenesis geneset, including targetable genes like VEGF and FGFR. Also, an MYO (CL3) subtype was identified, with myogenesis-related genes. Of note, TIL (tumor infiltrating lymphocytes) and LAR quantification using IHC were associated with respective ARTEMIS subtypes. Finally, the IM subtype was significantly associated with higher rates of RCB 0-I and the M (CL4) subtype was associated with higher rates of RCB II-III, irrespective of the neoadjuvant treatment regimen. ARTEMIS subtypes are a novel classification system for TNBC that is focused on therapeutic translation. Further, we show a possibility to classify previously un-classified (UNS) tumors, which will be validated using additional cohorts (TCGA/METABRIC). Citation Format: Seth S, Huo L, Rauch G, Lau R, Gilcrease M, Adrada B, Piwnica-Worms H, Symmans WF, Draetta G, Futreal AP, Moulder S, Chang JT. Towards a therapeutically relevant subtyping scheme for triple-negative breast cancer (TNBC), profiling results from A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival (ARTEMIS) [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 P3-07-01.