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地舒单抗治疗与乳腺癌患者循环肿瘤细胞缺失相关。

Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer.

机构信息

Gynecologic Cancer Center, University Hospital Basel, 4056, Basel, Switzerland.

Department of Medical Oncology, University Hospital Basel, 4056, Basel, Switzerland.

出版信息

Breast Cancer Res. 2018 Nov 20;20(1):141. doi: 10.1186/s13058-018-1067-y.

Abstract

BACKGROUND

The presence of circulating tumor cells (CTCs) in patients with breast cancer correlates to a bad prognosis. Yet, CTCs are detectable in only a minority of patients with progressive breast cancer, and factors that influence the abundance of CTCs remain elusive.

METHODS

We conducted CTC isolation and enumeration in a selected group of 73 consecutive patients characterized by progressive invasive breast cancer, high tumor load and treatment discontinuation at the time of CTC isolation. CTCs were quantified with the Parsortix microfluidic device. Clinicopathological variables, blood counts at the time of CTC isolation and detailed treatment history prior to blood sampling were evaluated for each patient.

RESULTS

Among 73 patients, we detected at least one CTC per 7.5 ml of blood in 34 (46%). Of these, 22 (65%) had single CTCs only, whereas 12 (35%) featured both single CTCs and CTC clusters. Treatment with the monoclonal antibody denosumab correlated with the absence of CTCs, both when considering all patients and when considering only those with bone metastasis. We also found that low red blood cell count was associated with the presence of CTCs, whereas high CA 15-3 tumor marker, high mean corpuscular volume, high white blood cell count and high mean platelet volume associated specifically with CTC clusters.

CONCLUSIONS

In addition to blood count correlatives to single and clustered CTCs, we found that denosumab treatment associates with most patients lacking CTCs from their peripheral circulation. Prospective studies will be needed to validate the involvement of denosumab in the prevention of CTC generation.

摘要

背景

乳腺癌患者循环肿瘤细胞(CTCs)的存在与预后不良相关。然而,在进展性乳腺癌患者中,只有少数患者可检测到 CTCs,并且影响 CTCs 丰度的因素仍难以捉摸。

方法

我们对 73 例连续进展性浸润性乳腺癌、高肿瘤负荷且在 CTC 分离时停止治疗的患者进行了 CTC 分离和计数。使用 Parsortix 微流控设备定量 CTCs。评估每位患者的临床病理变量、CTC 分离时的血细胞计数以及血液取样前的详细治疗史。

结果

在 73 例患者中,我们在 34 例(46%)患者中每 7.5ml 血液中至少检测到一个 CTC。其中,22 例(65%)仅存在单个 CTC,而 12 例(35%)既有单个 CTC 又有 CTC 簇。抗单克隆抗体地舒单抗的治疗与 CTCs 的缺失相关,既包括所有患者,也包括仅存在骨转移的患者。我们还发现,红细胞计数低与 CTCs 的存在相关,而 CA 15-3 肿瘤标志物高、平均红细胞体积高、白细胞计数高和平均血小板体积高与 CTC 簇特异性相关。

结论

除了与单个和簇状 CTC 相关的血细胞计数外,我们还发现地舒单抗治疗与大多数患者外周循环中缺乏 CTCs 相关。需要前瞻性研究来验证地舒单抗在预防 CTC 产生中的作用。

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