Abstract BS3-1: Manifestations and implications of subclonal alterations in metastatic breast cancer

Abstract

Abstract Clinical and pathological evidence for intratumoral heterogeneity (ITH) in breast cancer has long existed, however recent advances in genomic sequencing have revealed a remarkable depth and complexity to ITH. This is further magnified in the study of metastatic breast cancer where there has been significant expansion in the number of tumors as well as the selective pressures faced by individual tumor cells. The near universality of such heterogeneity has led many to question whether ITH is of any biologic or clinical significance or it is simply an intrinsic property of a large population of cancer cells with unstable genomes. We would posit that the significance of ITH can be observed by understanding the pressures that may have generated them. In particular, drug therapy such as anti-estrogen or HER2 targeted therapy can influence the manifestation of ITH. This can reveal underlying vulnerabilities and resiliencies in different cases. In this talk, we will review the evidence that ITH exists for important drivers of breast cancer growth, elucidate the biologic and clinical significance of such findings with a focus on resistance to hormone therapy, and discuss potential strategies to overcome it. Citation Format: Chandarlapaty S. Manifestations and implications of subclonal alterations in metastatic breast cancer [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 BS3-1.