Breast Cancer Research and Treatment

, Volume 150, Issue 2, pp 299–307 | Cite as

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

  • Chiya Oshiro
  • Naofumi KagaraEmail author
  • Yasuto Naoi
  • Masafumi Shimoda
  • Atsushi Shimomura
  • Naomi Maruyama
  • Kenzo Shimazu
  • Seung Jin Kim
  • Shinzaburo Noguchi
Preclinical Study


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 (ctDNAhigh) and ctDNA-low (ctDNAlow) groups based on the median. The ctDNAhigh 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 ctDNAlow patient and ctDNA-free patient group. Multivariate analysis revealed that ctDNAhigh 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 ctDNAhigh but not ctDNAlow status is a significant and independent prognostic factor for primary breast cancer patients.


Breast cancer PIK3CA mutation ctDNA dPCR Prognosis 



This work was supported in part by Grants-in-Aid from the Knowledge Cluster Initiative of the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Conflict of interest

The authors of this study have no conflicts of interest and no financial disclosures to make.

Supplementary material

10549_2015_3322_MOESM1_ESM.pdf (346 kb)
Supplementary material 1 (PDF 346 kb)
10549_2015_3322_MOESM2_ESM.pdf (77 kb)
Supplementary material 2 (PDF 77 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chiya Oshiro
    • 1
  • Naofumi Kagara
    • 1
    Email author
  • Yasuto Naoi
    • 1
  • Masafumi Shimoda
    • 1
  • Atsushi Shimomura
    • 1
  • Naomi Maruyama
    • 1
  • Kenzo Shimazu
    • 1
  • Seung Jin Kim
    • 1
  • Shinzaburo Noguchi
    • 1
  1. 1.Department of Breast and Endocrine SurgeryOsaka University Graduate School of MedicineSuita-shiJapan

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