Background

Patients with breast cancer (BC) at advanced stages have poor outcomes because of high rate of recurrence and metastasis. Biomarkers for predicting prognosis remain to be explored. This study aimed to evaluate the relationships between circulating tumor cells (CTCs) and outcomes of BC patients.

Patients and methods

A total of 50 female were enrolled in this study. Their diagnoses were determined by clinical characteristics, image data, and clinical pathology. CTC subtypes and TOP2A gene expression on CTCs were detected by CanPatrol™ technology and triple color in situ RNA hybridization (RNA-ISH), which divided into epithelial CTCs (eCTCs), mesenchymal CTCs (MCTCs), and hybrid CTCs (HCTCs) based on their surface markers. Hormone receptor, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, was measured by immunohistochemistry (IHC) method before treatment. The risk factors for predicting recurrence and metastasis were calculated by COX risk regression model. The progression-free survival (PFS) of patients was determined using Kaplan–Meier survival curve.

Results

The patients with a large tumor size (≥ 3 cm) and advanced tumor node metastasis (TNM) stages had high total CTCs (TCTCs) (P < 0.05). These patients also had high TOP2A expression level. COX risk regression analysis indicated that TOP2A expression levels in TCTCs, ER + , HER-2 + , and TNM stages were critical risk factors for recurrence and metastasis of patients (P < 0.05). The PFS of patients with ≥ 5 TCTCs, ≥ 3 HCTCs, and positive TOP2A expression in ≥ 3 TCTCs was significantly longer than that in patient with < 5 TCTCs, < 3 HCTCs, and TOP2A expression in < 3 TCTCs (P < 0.05). In contrast, the PFS of patients with positive hormone receptors (ER + , PR + , HER-2 +) also was dramatically lived longer than that in patients with negative hormone receptor expression.

Conclusions

High TCTC, HCTCs, and positive TOP2A gene expression on CTCs were critical biomarkers for predicting outcomes of BC patients. Positive hormone receptor expression in BC patients has significant favor PFS.

中文翻译：

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循环肿瘤细胞TOP2A基因表达与乳腺癌患者化疗耐药的相关性研究

背景

晚期乳腺癌（BC）患者由于复发和转移率高，预后较差。用于预测预后的生物标志物仍有待探索。本研究旨在评估循环肿瘤细胞 (CTC) 与 BC 患者预后之间的关系。

患者和方法

共有 50 名女性参加了这项研究。他们的诊断是根据临床特征、图像数据和临床病理学确定的。采用CanPatrol™技术和三色原位RNA杂交（RNA-ISH）检测CTC亚型和CTC上TOP2A基因表达，根据CTC分为上皮CTC（eCTC）、间质CTC（MCTC）和混合CTC（HCTC）。他们的表面标记。治疗前采用免疫组化（IHC）法测定激素受体，包括雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）的表达量。采用COX风险回归模型计算预测复发和转移的危险因素。使用Kaplan-Meier生存曲线确定患者的无进展生存期（PFS）。

结果

肿瘤体积较大（≥3 cm）且TNM分期晚期的患者总CTC（TCTC）较高（P  < 0.05）。这些患者的TOP2A表达水平也很高。 COX风险回归分析显示， TCTCs、ER+、HER-2+、TNM分期中TOP2A表达水平是患者复发转移的关键危险因素（P  <0.05）。 TCTC ≥ 5 个、HCTC ≥ 3 个、且 TCTC ≥ 3 个TOP2A表达阳性的患者的 PFS显着长于 TCTC < 5 个、HCTC < 3 个、TCTC 中TOP2A表达 < 3 个的患者（ P  < 0.05）。相比之下，激素受体（ER+、PR+、HER-2+）阳性的患者的 PFS 也比激素受体表达阴性的患者显着延长。

结论

高 TCTC、HCTC 和CTC 上的TOP2A基因阳性表达是预测 BC 患者预后的关键生物标志物。 BC患者中激素受体表达阳性对PFS有显着影响。