Open AccessPrognostic role of PIK 3 CA mutations of cell‐free DNA in early‐stage triple negative breast cancer
Author(s) -
Takeshita Takashi,
Yamamoto Yutaka,
YamamotoIbusuki Mutsuko,
Inao Toko,
Sueta Aiko,
Fujiwara Saori,
Omoto Yoko,
Iwase Hirotaka
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12813
Subject(s) - breast cancer , biomarker , triple negative breast cancer , cancer research , mutation , cancer , gene , biology , oncogene , microbiology and biotechnology , medicine , cell cycle , genetics
PIK 3 CA is an oncogene that encodes the p110α component of phosphatidylinositol 3‐kinase ( PI 3K); it is the second most frequently mutated gene following the TP 53 gene. In the clinical setting, PIK 3 CA mutations may have favorable prognostic value for hormone receptor‐positive breast cancer patients and, during the past few years, PIK 3 CA mutations of cell‐free DNA (cf DNA ) have attracted attention as a potential noninvasive biomarker of cancer. However, there are few reports on the clinical implications of PIK 3 CA mutations for TNBC patients. We investigated the PIK 3 CA major mutation status of cf DNA as a noninvasive biomarker of cancer using droplet digital polymerase chain reaction (dd PCR ), which has high level sensitivity and specificity for cancer mutation, in early‐stage 49 triple negative breast cancer ( TNBC ) patients. A total of 12 (24.4%) of 49 patients had PIK 3 CA mutations of cf DNA . In a median follow up of 54.4 months, the presence of PIK 3 CA mutations of cf DNA had significant impacts on relapse‐free survival ( RFS ; P = 0.0072) and breast cancer‐specific survival ( BCSS ; P = 0.016), according to the log‐lank test. In a Cox proportional hazards model, the presence of PIK 3 CA mutations of cf DNA had significant prognostic value in the univariate and multivariate analysis. Additionally, the presence of PIK3CA mutations of cfDNA was significantly correlated with positive androgen receptor phosphorylated form depending on PI3K signaling pathway (pAR) which is independent favorable prognostic factors of TNBC. We demonstrated that the presence of PIK 3 CA major mutations of cf DNA could be a discriminatory predictor of RFS and BCSS in early‐stage TNBC patients and it was associated with PI3K pathway‐dependent AR phosphorylation.