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

ABSTRACT: PIK3CA is an oncogene that encodes the p110? 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.

SUBMITTER: Takeshita T

PROVIDER: S-EPMC4714688 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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

Takeshita Takashi T Yamamoto Yutaka Y Yamamoto-Ibusuki Mutsuko M Inao Toko T Sueta Aiko A Fujiwara Saori S Omoto Yoko Y Iwase Hirotaka H

Cancer science 20151030 11

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 implicat ...[more]

PMID: 26353837

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Project description:Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621-0.757; C-index for OS: 0.728, 95% CI: 0.654-0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

Dataset Information

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

Publications

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

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