Abstract ES4-3: The genomic landscape of endocrine-resistant metastatic breast cancer

Abstract

Abstract Recent efforts to characterize the genomes of metastatic breast cancers hold promise for understanding the evolution of the disease through comparative analyses with primary breast cancers. However, these analyses have proven challenging due to the number of differences including differences in tumor representation and spatial tumor heterogeneity resulting in less accurate representation of metastatic disease, and temporal heterogeneity often due to the selective pressures of treatments, all of which may independently alter the ongoing natural evolution of the tumor containing disrupted DNA and/or DNA repair processes. Advances in genomic analyses and large repositories of samples with detailed clinical annotation have enabled rational deconvolution of these datasets, revealing novel insights into the unique drivers shaping advanced and lethal disease. In particular, large cohorts of patients with exposure to therapy with hormonal therapy has enabled the identification of specific genomic alterations that can promote resistance to hormonal therapy. This classification of genomic mechanisms of endocrine resistance has helped uncover the forces that shape the hormone dependence of ER+ breast cancer while also identifying new therapeutic targets with the promise to treat or even prevent endocrine resistant disease. In this presentation, we will review the genomic features of endocrine resistance metastatic breast cancer, detail evidence for (or against) specific alterations as likely mechanisms of resistance to endocrine therapy and describe next steps for clinical utilization of genomic information for the management of this disease. Citation Format: P Razavi. The genomic landscape of endocrine-resistant metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES4-3.