Plasma cell-free DNA chromosomal instability analysis by low-pass whole-genome sequencing to monitor breast cancer relapse | SpringerLink

Plasma cell-free DNA chromosomal instability analysis by low-pass whole-genome sequencing to monitor breast cancer relapse | SpringerLink

Plasma cell-free DNA chromosomal instability analysis by low-pass whole-genome sequencing to monitor breast cancer relapse

• Huanhuan Zhou, 
• Xiao-Jia Wang, 
• Xiyi Jiang, 
• Ziliang Qian, 
• Tianhui Chen, 
• Yue Hu, 
• Zhan-Hong Chen, 
• Yun Gao, 
• Rong Wang, 
• Wei-Wu Ye & 
• Wen-Ming Cao 

Breast Cancer Research and Treatment volume 178, pages63–73(2019)Cite this article

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Abstract

Background

Chromosomal instabilities (CIN) of plasma cell-free DNA (cfDNA) are common in breast cancer. We aimed to investigate the value of cfDNA CIN in monitoring the breast cancer relapse and additionally to compare it with the traditional biomarkers (CA15-3 and CEA).

Methods

Overall 62 recurrent breast cancer patients and 20 healthy controls were recruited. Low-pass whole-genome sequencing (LPWGS) was performed to detect cfDNA CIN. A CIN score was calculated. The performance of CA15-3, CEA, and CIN score in monitoring the recurrence was investigated with receiver operating characteristic (ROC) curve and the area under curve (AUC). Multivariable Cox proportional hazard model was established to analyze the correlations between copy number gain/loss and disease-free survival (DFS).

Results

cfDNA CIN achieved the positive rate of 77.6% [(95% confidence interval (CI) 73.4–95.3%)] among recurrent breast cancer patients, with an AUC value of 0.933, superior to CA15-3 (positive rate: 38.7%; AUC: 0.864) and CEA (positive rate: 41.93%; AUC: 0.878) (P < 0.01). The combination of cfDNA CIN with two biomarkers further increased the positive rate to 88.7% (95% confidence interval 77.5–95.0%). cfDNA CIN achieved better performance in patients with shorter DFS (≤ 41 months), with an AUC value of 0.975.

Conclusions

cfDNA CIN yields a higher accuracy in monitoring breast cancer recurrence compared to traditional biomarkers (CA15-3 and CEA), especially for biomarker-negative patients. The combination of cfDNA CIN to traditional biomarkers further improved the detection rate of recurrence, which may provide a new method for monitoring the early relapse of breast cancer, though further investigations are warranted.