Detection of the PIK3CA Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer ()
Affiliation(s)
1Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
2Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
3Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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.
Share and Cite:
Sato, A. , Tanabe, M. , Tsuboi, Y. , Ikemura, M. , Tada, K. , Seto, Y. and Murakami, Y. (2018) Detection of the
PIK3CA Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer.
Journal of Cancer Therapy,
9, 42-54. doi:
10.4236/jct.2018.91006.