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KMID : 1134120200230040373
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Journal of Breast Cancer
2020 Volume.23 No. 4 p.373 ~ p.384
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Analysis of Circulating Tumor DNA to Predict Neoadjuvant Therapy Effectiveness and Breast Cancer Recurrence
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Hao Shuai
Tian Wuguo
Zhao Jianjie
Chen Yi
Zhang Xiaohua
Gao Bo
He Yujun
Luo Donglin
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Abstract
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Purpose: Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied.
Methods: We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes.
Results: In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence.
Conclusion: Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.
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KEYWORD
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Breast neoplasms, Circulating tumor DNA, Neoadjuvant therapy, Recurrence
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