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辅助放疗对原发性非转移性乳腺癌患者循环上皮肿瘤细胞和循环癌干细胞的影响

Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer.

作者信息

Schott Dorothea Sonja, Pizon Monika, Pachmann Ulrich, Pachmann Katharina, Schobert Rainer, Wittig Andrea, Mäurer Matthias

机构信息

Transfusion Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany.

Organic Chemistry University of Bayreuth, Bayreuth, Germany.

出版信息

Transl Oncol. 2021 Mar;14(3):101009. doi: 10.1016/j.tranon.2021.101009. Epub 2021 Jan 14.

Abstract

BACKGROUND

There is an unmet need to identify biomarkers that directly reflect response to adjuvant radiotherapy (RT). Circulating epithelial tumor cells (CETCs) represent the liquid component of solid tumors and are responsible for metastatic relapse. CETC subsets with cancer stem cell characteristics, circulating cancer stem cells (cCSCs), play a pivotal role in the metastatic cascade. Monitoring the most aggressive subpopulation of CETCs could reflect the aggressiveness of the remaining tumor burden. There is limited data on the detection and monitoring changes in CETC and cCSC numbers during RT in early breast cancer.

METHODS

CETC numbers were analyzed prior to, at midterm and at the end of RT in 52 primary non-metastatic breast cancer patients. Hormone receptor status was determined in CETCs prior to and at the end of RT. For the identification of cCSCs cell suspensions from the peripheral blood of patients were cultured in vitro under conditions favoring growth of tumorspheres.

RESULTS

Hormone receptor status in CETCs before RT was comparable to that in primary tumor tissue. Prior to RT numbers of CETCs correlated with aggressiveness of primary tumors. cCSCs could be successfully identified and monitored during RT. Prior to RT patients treated with neoadjuvant chemotherapy had significantly higher numbers of CETCs and tumorspheres compared to patients after adjuvant chemotherapy. During RT, the number of CETCs decreased continuously in patients after neoadjuvant chemotherapy but not after adjuvant chemotherapy.

CONCLUSION

Monitoring the number of CETCs and the CETC subset with cancer stem cell properties during RT may provide additional clinically useful prognostic information.

摘要

背景

识别直接反映辅助放疗(RT)反应的生物标志物仍存在未满足的需求。循环上皮肿瘤细胞(CETCs)代表实体瘤的液体成分,是转移复发的原因。具有癌症干细胞特征的CETC亚群,即循环癌症干细胞(cCSCs),在转移级联反应中起关键作用。监测CETCs中最具侵袭性的亚群可以反映剩余肿瘤负荷的侵袭性。关于早期乳腺癌放疗期间CETC和cCSC数量的检测及变化监测的数据有限。

方法

对52例原发性非转移性乳腺癌患者在放疗前、放疗中期和放疗结束时的CETC数量进行分析。在放疗前和放疗结束时测定CETCs中的激素受体状态。为了鉴定cCSCs,将患者外周血的细胞悬液在有利于肿瘤球生长的条件下进行体外培养。

结果

放疗前CETCs中的激素受体状态与原发性肿瘤组织中的相当。放疗前CETCs的数量与原发性肿瘤的侵袭性相关。在放疗期间可以成功鉴定和监测cCSCs。放疗前,与接受辅助化疗后的患者相比,接受新辅助化疗的患者的CETCs和肿瘤球数量明显更高。在放疗期间,新辅助化疗后的患者的CETCs数量持续下降,但辅助化疗后的患者则不然。

结论

在放疗期间监测CETCs数量以及具有癌症干细胞特性的CETC亚群可能会提供额外的临床有用预后信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e09e/7811056/dd4c9da65c60/gr1.jpg

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