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Diehl, F., Schmidt, K., Choti, M.A., Romans, K., Goodman, S., Li, M., Thornton, K., Agrawal, N., Sokoll, L., Szabo, S.A., Kinzler, K.W., Vogelstein, B. and Diaz, L.A. (2008) Circulating Mutant DNA to Assess Tumor Dynamics. Nature Medicine, 14, 985-990.
https://doi.org/10.1038/nm.1789

has been cited by the following article:

• TITLE: Detection of the PIK3CA Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer

  AUTHORS: Ayaka Sato, Masahiko Tanabe, Yumi Tsuboi, Masako Ikemura, Keiichiro Tada, Yasuyuki Seto, Yoshinori Murakami

  KEYWORDS: Early-Stage Breast Cancer, PIK3CA, Circulating Tumor DNA, Plasma, Droplet Digital PCR

  JOURNAL NAME: Journal of Cancer Therapy, Vol.9 No.1, January 26, 2018

  ABSTRACT: Objectives: Circulating tumor DNA (ctDNA) is shown to provide the real-time genomic information of metastatic breast cancer. This study elucidates the clinico-pathological significance of ctDNA in early-stage breast cancer using the PIK3CA mutation as an indicator. Materials and Methods: Twenty-seven primary breast cancers without metastasis were surgically resected and pathologically diagnosed at the University of Tokyo Hospital, Japan. Genomic DNA of primary tumor was extracted from formalin-fixed and paraffin-embedded specimens. ctDNA was extracted from fresh-frozen plasma from patients. The PIK3CA mutations at E542K, E545K and H1047R were examined by Sanger sequencing or droplet digital PCR in 27 tumors and pre- and post-surgery plasma. Results: The PIK3CA mutations were detected in 13 (48%) of 27 primary tumors. These mutations did not significantly correlate with specific clinico-pathological characteristics of tumors. When ctDNA was examined, 4 (33%) of 12 cases carrying the mutated PIK3CA showed the identical mutation in pre-surgery plasma and 2 (50%) of them showed the identical mutations in post-surgery plasma. Interestingly, in these 2 cases in pathological stages IIIA and IA, fractional abundance of the mutated PIK3CA alleles to the total alleles in pre-surgery ctDNA was around 1% or more and was higher than that of the other two cases without PIK3CA mutations in post-surgery ctDNA. Conclusions: The PIK3CA mutation in ctDNA is detectable even in a subset of early-stage breast cancer. Furthermore, fractional abundance of the mutated PIK3CA in pre-surgery ctDNA could provide a possible predictive indicator for tumor burden and for choosing the appropriate adjuvant treatment of breast cancer.