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Rigshospitalet - en del af Københavns Universitetshospital
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Correlation between circulating cell-free PIK3CA tumor DNA levels and treatment response in patients with PIK3CA-mutated metastatic breast cancer

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  • Annette R Kodahl
  • Sidse Ehmsen
  • Niels Pallisgaard
  • Anne M B Jylling
  • Jeanette D Jensen
  • Anne-Vibeke Laenkholm
  • Ann S Knoop
  • Henrik J Ditzel
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Liquid biopsies focusing on the analysis of cell-free circulating tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance, and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly sensitive, optimized droplet digital PCR (ddPCR) assay. We found 83% of patients with PIK3CA mutation in the metastatic tumor tissue also had detectable PIK3CA mutations in serum ctDNA. Patients lacking the PIK3CA mutation in corresponding serum ctDNA all had nonvisceral metastatic disease. Four patients with detectable PIK3CA-mutated ctDNA were followed with an additional serum sample during oncological treatment. In all cases, changes in PIK3CA ctDNA level correlated with treatment response. Our results showed high concordance between detection of PIK3CA mutations in tumor tissue and in corresponding serum ctDNA and suggest that serum samples from patients with advanced breast cancer and ddPCR may be used for PIK3CA mutation status assessment to complement imaging techniques as an early marker of treatment response.

OriginalsprogEngelsk
TidsskriftMolecular Oncology
Vol/bind12
Udgave nummer6
Sider (fra-til)925-935
Antal sider11
ISSN1574-7891
DOI
StatusUdgivet - jun. 2018

ID: 54652818