Cancer Res Treat.  2023 Jan;55(1):145-154. 10.4143/crt.2022.001.

Analysis of PIK3CA Mutation Concordance and Frequency in Primary and Different Distant Metastatic Sites in Breast Cancer

  • 1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
  • 2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
  • 4Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 5Central Laboratory, LOGONE Bio-Convergence Research Foundation, Seoul, Korea
  • 6Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea


The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved.
Materials and Methods
Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20.
After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance.
The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.


Breast neoplasms; Molecular diagnostics; Neoplasm metastasis; Droplet digital PCR


  • Fig. 1 Study design. FFPE, formalin-fixed paraffin-embedded.

  • Fig. 2 Alteration of PIK3CA mutations (A) and molecular subtype classifications (B) between primary breast cancer and matched metastases in 49 patients with breast cancer. HER2, human epidermal growth factor receptor 2; ND, not detected; TNBC, triple-negative breast cancer.

  • Fig. 3 Mutations involving PIK3CA in metastatic sites of breast cancer. (A) Frequency of PIK3CA mutation in 33 patients who had PIK3CA mutation in the site of metastasis. In the case of multiple PIK3CA mutations, only the major mutation based on the mutation index (MI) was included. (B) Cases of multiple mutations in PIK3CA. The classification of major and minor mutations was based on MI (%). ABD, adaptor binding domain; RBD, ras-binding domain.

  • Fig. 4 PIK3CA mutation proportions of 89 patients with metastatic breast cancer by site of metastasis. Mosaic plots representing PIK3CA mutation proportion for the 89 patients of metastatic breast cancer by site of metastases. PIK3CA mutation screening was performed at the site of metastases using droplet digital polymerase chain reaction assays. p-values were calculated using chi-square tests.



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