Open AccessCorrelation between circulating cell‐free PIK 3 CA tumor DNA levels and treatment response in patients with PIK 3 CA ‐mutated metastatic breast cancer
Author(s) -
Kodahl Annette R.,
Ehmsen Sidse,
Pallisgaard Niels,
Jylling Anne M. B.,
Jensen Jeanette D.,
Lænkholm AnneVibeke,
Knoop Ann S.,
Ditzel Henrik J.
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12305
Subject(s) - digital polymerase chain reaction , liquid biopsy , oncogene , breast cancer , cancer research , metastatic breast cancer , concordance , mutation , cancer , biomarker , cell free fetal dna , circulating tumor cell , medicine , microbiology and biotechnology , biology , metastasis , polymerase chain reaction , cell cycle , gene , genetics , pregnancy , fetus , prenatal diagnosis
Liquid biopsies focusing on the analysis of cell‐free circulating tumor DNA (ct DNA ) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance, and monitoring of recurrence. Mutations in the oncogene, PIK 3 CA , are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI 3K‐selective inhibitor treatment. In this study, we analyzed the presence of PIK 3 CA mutations in formalin‐fixed, paraffin‐embedded, metastatic tissue and corresponding ct DNA from serum of patients with advanced breast cancer using a highly sensitive, optimized droplet digital PCR (dd PCR ) assay. We found 83% of patients with PIK 3 CA mutation in the metastatic tumor tissue also had detectable PIK 3 CA mutations in serum ct DNA . Patients lacking the PIK 3 CA mutation in corresponding serum ct DNA all had nonvisceral metastatic disease. Four patients with detectable PIK 3 CA ‐ mutated ct DNA were followed with an additional serum sample during oncological treatment. In all cases, changes in PIK 3 CA ct DNA level correlated with treatment response. Our results showed high concordance between detection of PIK 3 CA mutations in tumor tissue and in corresponding serum ct DNA and suggest that serum samples from patients with advanced breast cancer and dd PCR may be used for PIK 3 CA mutation status assessment to complement imaging techniques as an early marker of treatment response.