Use of Liquid Biopsy to Detect PIK3CA Mutation in Metastatic Breast Cancer

J Nippon Med Sch. 2022 Mar 11;89(1):66-71. doi: 10.1272/jnms.JNMS.2022_89-107. Epub 2021 Mar 9.

Abstract

Background: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer.

Methods: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR.

Results: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors.

Conclusions: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

Keywords: breast cancer; genetic screening; liquid biopsy.

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Circulating Tumor DNA* / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Female
  • Humans
  • Liquid Biopsy
  • Mutation

Substances

  • Circulating Tumor DNA
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human