Niwinska Anna, Bałabas Aneta, Kulecka Maria, Kluska Anna, Piątkowska Magdalena, Paziewska Agnieszka, Pyśniak Kazimiera, Olszewski Wojciech, Mikula Michał, Ostrowski Jerzy
Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
Diagnostics (Basel). 2020 Jul 28;10(8):523. doi: 10.3390/diagnostics10080523.
Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected from six healthy women and 37 patients with breast cancer (18 and 19 with stage III and IV tumors, respectively). CfDNA was assessed using the Oncomine Pan-Cancer Cell-Free Assay. In cfDNA samples from patients with BC, 1112 variants were identified, with only a few recurrent or hotspot mutations within specific regions of cancer genes. Of 65 potentially pathogenic variants detected in tumors, only 19 were also discovered in at least one blood sample. The allele frequencies of detected variants (VAFs) were <1% in cfDNA from all controls and patients with stage III BC, and 24/85 (28.2%) variants had VAFs > 1% in only 8 of 25 (32%) patients with stage IV BC. Copy number variations (CNVs) spanning , , , , , , and were found in 1 of 12 (8%) and 8 of 25 (32%) patients with stage III and IV tumors, respectively. In healthy controls and patients without BC progression after treatment, VAFs were <1%, while in patients with metastatic disease and/or more advanced genomic alterations, VAFs > 1% and/or CNV were detected in approximately 30%. Therefore, most patients with stage IV BC could not be distinguished from those with stage III disease following therapy, based on liquid biopsy results.
最近，液体活检已成为一种监测肿瘤疾病进展和治疗效果的工具。在本研究中，我们旨在确定液体活检相对于传统肿瘤治疗后监测的临床效用。从6名健康女性和37名乳腺癌患者（分别为18名和19名III期和IV期肿瘤患者）中收集血浆游离（cf）DNA。使用Oncomine泛癌游离细胞检测法评估cfDNA。在乳腺癌患者的cfDNA样本中，鉴定出1112个变异，在癌症基因的特定区域内只有少数复发性或热点突变。在肿瘤中检测到的65个潜在致病变异中，只有19个也在至少一份血液样本中被发现。在所有对照和III期乳腺癌患者的cfDNA中，检测到的变异的等位基因频率（VAF）<1%，在25名IV期乳腺癌患者中的8名（32%）患者中，只有24/85（28.2%）个变异的VAF>1%。在III期和IV期肿瘤患者中，分别有1/12（8%）和8/25（32%）的患者发现了跨越、、、、、和的拷贝数变异（CNV）。在健康对照和治疗后无乳腺癌进展的患者中，VAF<1%，而在有转移性疾病和/或更晚期基因组改变的患者中，约30%检测到VAF>1%和/或CNV。因此，根据液体活检结果，大多数IV期乳腺癌患者与III期疾病患者无法区分。
