Beaubier, Nike

PURPOSETissue-based next-generation sequencing (NGS) in metastatic breast cancer (mBC) is limited by the inability to noninvasively track tumor evolution. Cell-free DNA (cfDNA) NGS has made sequential testing feasible; however, the relationship between cfDNA and tissue-based testing in mBC is not well understood. Here, we evaluate concordance between tissue and cfDNA NGS relative to cfDNA sampling frequency in a large, clinically annotated mBC data set.METHODSTempus LENS was used to analyze deidentified records of mBC cases with Tempus xT (tissue) and xF (cfDNA) sequencing results. Then, various metrics of concordance were assessed within overlapping probe regions of the tissue and cfDNA assays (104 genes), focusing on pathogenic variants. Variant allele frequencies of discordant and concordant pathogenic variants were also compared. Analyses were stratified by mBC subtype and time between tests.RESULTSRecords from 300 paired tissue and liquid biopsies were analyzed. Median time between tissue and blood collection was 78.5 days (standard deviation = 642.99). The median number of pathogenic variants/patient was one for cfDNA and two for tissue. Across the cohort, 77.8% of pathogenic tissue variants were found in cfDNA and 75.7% of pathogenic cfDNA variants were found in tissue when tests were ≤ 7 days apart, which decreased to 50.3% and 51.8%, respectively, for > 365 days. Furthermore, the median patient-level variant concordance was 67% when tests were ≤7 days apart and 30%-37% when > 30 days. The median variant allele frequencies of discordant variants were generally lower than those of concordant variants within the same time frame.CONCLUSIONWe observed high concordances between tissue and cfDNA results that generally decreased with longer durations between tests. Thus, cfDNA NGS reliably measures tissue genomics and is likely beneficial for longitudinal monitoring of molecular changes in mBC.

Abstract Genomic testing has transformed clinical care in metastatic breast cancer. Cell-free DNA (cfDNA) has made sequential testing feasible, however, concordance between tissue and cfDNA, sensitivity of cfDNA, and optimal sampling frequency have not been examined on large data sets with clinical annotation. Of the 648 genes in the tissue NGS Tempus xT assay, 105 genes are also included in the Tempus xF cfDNA plasma-based test. Both platforms are run on Illumina and detect SNVs, indels, CNVs, and rearrangements/fusions with high sensitivity and specificity (>90%). This study used the Tempus Labs LENS™ tool to identify the most recent ~3,300 metastatic breast cancer patients who underwent clinical testing and had either tissue-based testing, cfDNA testing or both. Of the 212 patients with xF and xT testing, 87 had xT before xF, 135 had xF before xT, and 7 had the testing performed at the same time. The most common pathogenic germline versus somatic alterations on tissue-based testing and their concordance will also be reported. In summary, this data suggests a variable amount of concordance between tissue-based and plasma-based assays. Timing of assay performance and inclusion of germline DNA might play an important role in contributing to these differences which need further exploration. Table: Count of Reported Variants and xT/xF Concordance by GeneSomatic GenesxF frequency (n)xT frequency(n)Concordance Between xF and xTTP5313911043%PIK3CA848058%ESR1584141%BRCA238217%ERBB2372629%NF1322113%RB1272416%ATM30165%GATA3213441%FGFR13353%PTEN193036%ARID1A251823% Citation Format: Minetta Liu, Jeff Schaffer, Aneta Piwowarczyk, Nike Beaubier, Kimberly Blackwell, Ben Park. Concordance and use patterns of tissue and cell-free based genomic testing in metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-12.