Prognostic role of PIK3CA mutations of cell-free DNA in early-stage triple negative breast cancer.
PIK3CA is an oncogene that encodes the p110α component of phosphatidylinositol 3-kinase (PI3K); it is the second most frequently mutated gene following the TP53 gene. In the clinical setting, PIK3CA mutations may have favorable prognostic value for hormone receptor-positive breast cancer patients and, during the past few years, PIK3CA mutations of cell-free DNA (cfDNA) have attracted attention as a potential noninvasive biomarker of cancer. However, there are few reports on the clinical implications of PIK3CA mutations for TNBC patients. We investigated the PIK3CA major mutation status of cfDNA as a noninvasive biomarker of cancer using droplet digital polymerase chain reaction (ddPCR), 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 PIK3CA mutations of cfDNA. In a median follow up of 54.4 months, the presence of PIK3CA mutations of cfDNA 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 PIK3CA mutations of cfDNA 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 PIK3CA major mutations of cfDNA could be a discriminatory predictor of RFS and BCSS in early-stage TNBC patients and it was associated with PI3K pathway-dependent AR phosphorylation.
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
Takashi
T
Takeshita
Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Kumamoto, Japan.
Yutaka
Y
Yamamoto
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
Mutsuko
M
Yamamoto-Ibusuki
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
Toko
T
Inao
Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Kumamoto, Japan.
Aiko
A
Sueta
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
Saori
S
Fujiwara
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.|Department of Endocrinological and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoko
Y
Omoto
Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
Hirotaka
H
Iwase
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004247:DNA / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D016016:Proportional Hazards Models; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality
D014408:Biomarkers, Tumor; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
Androgen receptor; PIK3CA mutations of circulating cell-free DNA; androgen receptor phosphorylation; droplet digital PCR; triple negative breast cancer