Abstract MS1-2: New clinical approaches for TNBC

Abstract

Abstract Over the last decade, triple-negative breast cancer (TNBC) has been the subject of intense clinical investigation. Importantly, an improved understanding of the critical role of DNA damage repair deficiency in TNBC has led to effective therapeutic strategies to target BRCA1 and BRCA2 mutation-associated TNBCs with platinum chemotherapy agents and PARP inhibitors. A major area of increasing clinical relevance focuses on the treatment of BRCA1 and BRCA2 mutation-associated breast cancers after the development of resistance to platinum and PARP inhibitor therapy. Lurbinectedin, a novel marine derived DNA damaging agent, has shown activity in BRCA1 and BRCA2 mutation-associated cancers, including those with platinum resistance. While therapeutic strategies for TNBC patients with BRCA1 and BRCA2 mutations have increased, most TNBC patients lack an underlying germline mutation in these genes and continue to have high unmet clinical need. Multiple lines of investigation are currently underway. Androgen receptor (AR) blockade has shown preliminary proof-of-concept in AR expressing TNBCs. While monotherapy with PD-1/PD-L1 checkpoint inhibitors has shown modest activity in metastatic TNBC, multiple studies are exploring the role of these agents in combination with chemotherapy, targeted therapies and other immunotherapeutic agents. Given the high prevalence of TP53 mutations in TNBC, strategies to target additional cell cycle checkpoints including ATR, ATM, Wee1 and others may hold promise. Antibody-drug conjugates targeting Trop-2, LIV-1 and GPNMB expressing TNBCs have also shown clinical activity and are advancing in clinical development. Citation Format: Telli M. New clinical approaches for TNBC [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr MS1-2.