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Life sciences · Journal article
npj Breast Cancer · October 20, 2026
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As biomarker-driven therapies are available for hormone receptor-positive (HR+) metastatic breast cancer (MBC), identification of actionable alterations is critical for determining the optimal therapy. Both tissue and plasma ctDNA next-generation sequencing (NGS) assays can reveal actionable alterations, but the concordance between these tests has not been established. In this retrospective cohort study of 367 patients with paired tumor tissue and ctDNA NGS, agreement between tissue and ctDNA testing was high across all actionable genes. Concordance was highest in PIK3CA and AKT1 and lower in ESR1 (higher detection in ctDNA) and PTEN (higher detection in tissue). ctDNA NGS alone identified all actionable genes in 88% of patients, though sensitivity was reduced when ctDNA fraction was low. This study represents one of the largest studies of tissue-ctDNA concordance in MBC, and establishes plasma ctDNA NGS as an effective, non-invasive alternative to tissue NGS for the detection of actionable alterations in HR+ MBC.