Abstract ED9-2A: Can ctDNA substitute tissue testing

Abstract Circulating tumor DNA (ctDNA) is at the forefront of liquid biopsy technology. A key advantage of ctDNA is being able to achieve genomic profiling from a blood test rather than from a more invasive tissue biopsy, reducing risk and discomfort for patients as well as costs and logistical complexity. Increasing evidence supports ctDNA as a useful clinical tool in specific indications, for example in the detection of PIK3CA mutations to identify patients suitable for alpelisib plus fulvestrant.The expectation is that indications for routine ctDNA testing will expand as more data become available and ctDNA is embedded into clinical trials and paired with novel therapies. Biological and technical factors both contribute to the feasibility of ctDNA expansion into the clinic. Representation of heterogeneity might be a key strength of ctDNA analysis over tumour biopsy analysis, as sampling the circulation compartment can in principle allow representation of a wider array of disease sites than a tumor sample acquired with a single needle. However, the factors influencing how different metastases might contribute to the circulating compartment are poorly understood, presenting a challenge to clinical interpretation. Moreover, the limit of detection of ctDNA assays, the timing of treatment and stochastic effects can contribute to uncertainty, particularly in the interpretation of negative results. Recent work analyzing tumor mutational burden using ctDNA has highlighted these challenges as applied to biomarker development. Circulating tumour DNA is likely to complement tissue biopsy in the future, and may substitute tumor biopsy in specific indications supported by the data. Ultimately, clinical utility for different ctDNA indications, as opposed to tissue biopsy, will need ongoing confirmation within clinical trials. Citation Format: Ben O’Leary. Can ctDNA substitute tissue testing [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-2A.