PIK3CA mutations in serum DNA are predictive of recurrence in primary breast cancer patients

Breast Cancer Res Treat. 2015 Apr;150(2):299-307. doi: 10.1007/s10549-015-3322-6. Epub 2015 Mar 4.


We attempted to develop a highly sensitive and specific method for the detection of circulating tumor DNA (ctDNA) using a digital PCR (dPCR) assay for PIK3CA mutations (i.e., H1047R, E545K, and E542K) in primary breast cancer patients. The sensitivity of the dPCR assay for the mutant alleles was examined using cell lines with PIK3CA mutations and proved to be 0.01 %. Serum samples were collected pre-operatively from 313 stage I-III breast cancer patients, of whom 110 were found to have PIK3CA mutant tumors. The serum samples from these patients with PIK3CA mutant tumors were subjected to the dPCR assay, and 25 (22.7 %) were found to be positive. No PIK3CA mutant ctDNA was detected in the serum samples of 50 healthy women and 30 breast cancer patients with PIK3CA non-mutant tumors. The patients with PIK3CA mutant ctDNA were dichotomized into mutant ctDNA-high (ctDNA(high)) and ctDNA-low (ctDNA(low)) groups based on the median. The ctDNA(high) patients exhibited significantly shorter recurrence-free survival (RFS; P = 0.0002) and overall survival rates (OS; P = 0.0048) compared to those exhibited by the combined ctDNA(low) patient and ctDNA-free patient group. Multivariate analysis revealed that ctDNA(high) status significantly predicted poor RFS and OS and did so independently of conventional histological parameters. These results suggest that dPCR is a highly sensitive and specific method for the detection of PIK3CA mutant ctDNA and that ctDNA(high) but not ctDNA(low) status is a significant and independent prognostic factor for primary breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Case-Control Studies
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Phosphatidylinositol 3-Kinases / blood
  • Phosphatidylinositol 3-Kinases / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • Sensitivity and Specificity


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