SY27-2 - The development of TNBC treatment through overcoming heterogeneity

Abstract

The treatment of TNBC is challenging due to the lack of effective treatments except for chemotherapies. Various research has evaluated TNBC's heterogeneity, establishing a consensus that TNBC is not a single unit but rather a biologically heterogeneous group. To seek optimal treatments, we have tried to divide the heterogeneous TNBC into homogeneous subtypes or identified mutations that have the potential to be therapeutic targets. These findings are reduced in the clinic to developing and conducting clinical trials focused on the molecularly targeted therapies. To overcome TNBC heterogeneity and seek optimal treatments, we cannot ignore biological features and must establish biology-oriented treatment strategies. Lehmann et al. identified seven molecular subtypes--basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), and unstable (UNS)--in 2011 on the basis of gene ontologies and differential gene expression and recently reported refinement TNBC 4 subtypes that removed IM and MSL subtypes because they confirmed these two subtypes represent tumors with substantial infiltrating lymphocytes and tumor-associated mesenchymal cells, respectively. We have confirmed these subtypes using the same methodology and indicated treatment strategies in each group. As a next step, to use this molecular information in a clinical setting, an identification tool for TNBC subtypes is under development. Further, evaluation of the mutations and mutation burden is an essential leading to the use of PARP inhibitor and immune checkpoint inhibitors. There are several new treatment agents based on antibody-drug conjugates have in TNBC. The learning objectives of this talk are as follows: 1. To understand the recent development of novel treatment approaches for TNBC 2. To acknowledge the importance of TNBC molecular subtyping and other new classification, which may impact the outcome of treatment developmet.