<i>ESR1</i> ctDNA testing: literature review and comparison of assays for <i>ESR1</i> mutation detection in advanced hormone receptor-positive breast cancer

Introduction Aromatase inhibitors (AI) plus CDK4/6 inhibitors are the current first-line standard-of-care for hormone receptor (HR)-positive/HER2-negative advanced breast cancer (ABC). However, mutations in ESR1 (ESR1m), the gene encoding the estrogen receptor, can drive resistance to AI; their detection in circulating tumor DNA from liquid biopsies may be used to guide treatment.Areas covered A literature search was performed using PubMed and Pharmaspectra to evaluate the current ESR1m testing landscape and compare analytical performance of commercially available ESR1m assays. Twenty-eight publications and 10 congress abstracts detailing assays for ESR1m detection in liquid biopsies were identified. These included four quantitative polymerase chain reaction (qPCR) ESR1m assays, four digital PCR (dPCR) ESR1m assays, and 12 next-generation sequencing (NGS)-based assays that all varied by ESR1m coverage, sensitivity, and specificity.Expert opinion A range of commercial assays are available for ESR1m detection in liquid biopsies from patients with HR-positive/HER2-negative ABC, and more are in development, with increasing clinical demand. qPCR, dPCR, and NGS assays can detect common ESR1m with differing sensitivity and specificity depending on the assay and amount of input DNA. Assay selection will vary depending on analytical performance, turnaround times, lab infrastructure and expertise, healthcare setting, and regional variation in market costs.