Prognostic role of PIK3CA mutations of cell‐free DNA in early‐stage triple negative breast cancer

Cancer Science

Takashi Takeshita²  Yutaka Yamamoto¹  Mutsuko Yamamoto-Ibusuki²  Toko Inao²  Aiko Sueta¹  Saori Fujiwara²  Yoko Omoto² 

[1] Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Kumamoto, Japan;Department of Breast and Endocrine surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

关键词: Androgen receptor;    androgen receptor phosphorylation;    droplet digital PCR;    PIK3CA mutations of circulating cell‐free DNA;    triple negative breast cancer;   

DOI  :  10.1111/cas.12813

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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