Eva Valentina Klocker, Nina Dobrić, Ricarda Graf, Christine Beichler, Dominik Hlauschek, Christoph Suppan, Lara Pancheri, Daniel Egle, Carmen Albertini, Rupert Bartsch, Angelika Martina Starzer, Philipp Jakob Jost, Gabriel Rinnerthaler, Ellen Heitzer, Nadia Dandachi, Marija Balic
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Clinical impact of single-gene vs. panel sequencing in advanced HR + /HER2- breast cancer: insights and implications.
Hormone receptor-positive (HR + )/HER2-negative (HER2 - ) breast cancer is the most common subtype, with biomarker-driven therapies improving outcomes. Circulating tumor DNA (ctDNA) analysis enables minimally invasive assessment of somatic alterations to guide therapy. However, assay choice impacts clinical utility, and access remains inconsistent. This study compares single-gene and panel-based sequencing for assessing PIK3CA mutations and broader genomic profiling. We conducted a prospective, multicenter study analyzing 161 plasma samples from 146 patients before initiating a new line of palliative therapy using the SiMSen-Seq (SSS) assay for PIK3CA hotspot mutations, the AVENIO ctDNA Expanded assay (77 genes) and mFAST-SeqS for tumor fraction estimation. High concordance (92.6%) was observed between SSS and AVENIO for PIK3CA mutations. AVENIO identified additional actionable alterations, including ESR1 (17.5%) and PI3K pathway alterations (40.6%), and together with tumor fraction estimation, improved interpretation of negative liquid biopsy findings. These findings support broader ctDNA profiling in clinical practice while highlighting accessibility challenges.
期刊介绍：
npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.
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