Department of Medical Oncology, Institut Jules Bordet, Brussels, Belgium.
PLoS One. 2011 Jan 10;6(1):e15624. doi: 10.1371/journal.pone.0015624.
Circulating Tumor Cells (CTCs) detection and phenotyping are currently evaluated in Breast Cancer (BC). Tumor cell dissemination has been suggested to occur early in BC progression. To interrogate dissemination in BC, we studied CTCs and HER2 expression on CTCs across the spectrum of BC staging.
Spiking experiments with 6 BC cell lines were performed and blood samples from healthy women and women with BC were analyzed for HER2-positive CTCs using the CellSearch®.
Based on BC cell lines experiments, HER2-positive CTCs were defined as CTCs with HER2 immunofluorescence intensity that was at least 2.5 times higher than the background. No HER2-positive CTC was detected in 42 women without BC (95% confidence interval (CI) 0-8.4%) whereas 4.1% (95%CI 1.4-11.4%) of 73 patients with ductal/lobular carcinoma in situ (DCIS/LCIS) had 1 HER2-positive CTC/22.5 mL, 7.9%, (95%CI 4.1-14.9%) of 101 women with non metastatic (M0) BC had ≥1 HER2-positive CTC/22.5 mL (median 1 cell, range 1-3 cells) and 35.9% (95%CI 22.7-51.9%) of 39 patients with metastatic BC had ≥1 HER2-positive CTC/7.5 mL (median 1.5 cells, range 1-42 cells). In CTC-positive women with DCIS/LCIS or M0 BC, HER2-positive CTCs were more commonly detected in HER2-positive (5 of 5 women) than HER2-negative BC (5 of 12 women) (p = 0.03).
HER2-positive CTCs were detected in DCIS/LCIS or M0 BC irrespective of the primary tumor HER2 status. Nevertheless, their presence was more common in women with HER2-positive disease. Monitoring of HER2 expression on CTCs might be useful in trials with anti-HER2 therapies.
循环肿瘤细胞（CTC）的检测和表型分析目前在乳腺癌（BC）中进行评估。肿瘤细胞的扩散已被认为在 BC 进展的早期发生。为了研究 BC 中的扩散，我们研究了整个 BC 分期范围内 CTC 及其 HER2 表达。
对 6 种 BC 细胞系进行了掺入实验，并使用 CellSearch®分析了健康女性和 BC 女性的血液样本中 HER2 阳性 CTC。
根据 BC 细胞系实验，HER2 阳性 CTC 定义为 HER2 免疫荧光强度至少比背景高 2.5 倍的 CTC。在 42 名没有 BC 的女性中未检测到 HER2 阳性 CTC（95%置信区间（CI）0-8.4%），而 73 名导管/小叶原位癌（DCIS/LCIS）患者中有 4.1%（95%CI 1.4-11.4%））有 1 个 HER2 阳性 CTC/22.5mL，101 名非转移性（M0）BC 女性中有 7.9%（95%CI 4.1-14.9%）≥1 个 HER2 阳性 CTC/22.5mL（中位数 1 个细胞，范围 1-3 个细胞），39 名转移性 BC 患者中有 35.9%（95%CI 22.7-51.9%）≥1 个 HER2 阳性 CTC/7.5mL（中位数 1.5 个细胞，范围 1-42 个细胞）。在具有 DCIS/LCIS 或 M0 BC 的 CTC 阳性女性中，HER2 阳性 CTC 更常见于 HER2 阳性（5/5 名女性）而非 HER2 阴性 BC（5/12 名女性）（p=0.03）。
无论原发性肿瘤 HER2 状态如何，在 DCIS/LCIS 或 M0 BC 中均可检测到 HER2 阳性 CTC。然而，它们在 HER2 阳性疾病女性中更为常见。监测 CTC 上的 HER2 表达可能对使用抗 HER2 治疗的试验有用。
