Abstract PD8-08: Characterization of spatial and temporal heterogeneity of ER positive metastatic breast cancer using serial biopsies

Abstract

Abstract Background: Metastatic breast cancer is characterized by a remarkable level of temporal and spatial heterogeneity. Management decisions based on a single tissue biopsy are therefore inherently limited by sampling bias and by dynamic changes in the receptor status and the mutational profile of the tumor. Methods: We characterized 41 serially enrolled patients on the tissue collection protocol DFHCC 13-416, who had ER+/HER2- breast cancer at the time of diagnosis of early stage disease. Results: 36 out of 41 patients (87.8%) had at least one biopsy in the metastatic setting. The number of biopsies in the metastatic setting ranged from one to seven. Two most frequently biopsied sites were liver (24.4%) and recurrent breast lesions (22.0%). Six out of 41 patients (14.6%) developed ER loss over the course of treatment. Estrogen receptor status conversions were noted in both the liver and in the recurrent breast lesions. PR loss was far more common, noted in 24 out of 41 patients (58.5%). Nine of these patients (21.9%) were PR negative at the time of diagnosis and an additional 15 patients (36.6%) lost PR expression during the course of their therapy. Median time to the loss of ER expression was 6.83 years from the initial diagnosis, while the median time to the loss of PR expression was 4.97 years, consistent with sequential decrease in ER dependence, resulting in loss of PR expression and increased dependence on other survival pathways. Genomic and transcriptomic profiling of all serially collected tissues with reconstruction of phylogenetic trees is ongoing and will be presented at the meeting. Conclusions: Compared to previously published reports, high proportion of patients in this cohort had their metastatic disease confirmed and subsequently followed by serial biopsies. In majority of patients, receptor status changes follow a predictable pattern starting with loss of PR expression, followed by complete loss of ER expression. Concomitant changes in the mutation status of both ER and other co-mutated genes, as well as any associated transcriptomic changes may shed light into new interdependencies and vulnerabilities associated with these dynamic receptor status changes. Citation Format: Read K. Allen, Christopher J. Pinto, Donna M. Fitzgerald, Tiffany G. Huynh, Christopher T. Chen, Dejan Juric. Characterization of spatial and temporal heterogeneity of ER positive metastatic breast cancer using serial biopsies [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 PD8-08.