Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
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DOI：
10.1007/s10549-020-05596-4
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发表时间：
2020-03-21
影响因子：
3.8
通讯作者：
Nanni, Oriana
中科院分区：
文献类型：
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作者：
Gennari, Alessandra;Foca, Flavia;Nanni, Oriana
目的通过一项前瞻性随机临床试验，比较化疗联合二甲双胍与单独化疗对转移性乳腺癌（MBC）患者循环肿瘤细胞（CTCs） IGF-1R表达的影响。方法在化疗开始时和化疗结束时收集CTCs。我们定制了自动样品制备和分析系统（CellSearch），用于检测IGF-1R的表达。通过单因素和多因素分析评估CTC计数和IGF-1R对PFS和OS的预后作用。结果126例随机患者中有72例进行了评估：57%的患者有>= 1个IGF-1R阳性CTC， 37.5%的患者有>= 4个IGF-1R阴性细胞；在单因素分析中，IGF-1R阴性CTC的数量与进展和死亡风险密切相关：HR分别为1.93 （P = 0.013）和3.65 (P = 0.001)；IGF-1R阳性CTCs数量与PFS或OS无相关性（P = 0.322和P = 0.840）。CTC计数的预后作用得到证实：PFS的HR为1.69,P = 0.042； OS的HR为2.80,P = 0.002。通过多因素分析，维持了IGF-1R阴性CTC数量对预后的影响，而未发现CTC计数或IGF-1R阳性细胞数量对预后的残余影响。结论：CTCs中IGF-1R的缺失与MBC患者的预后显著恶化相关。这一发现支持进一步评估IGF-1R在CTCs中的作用，以改善患者分层和实施新的靶向策略。临床试验注册：Clinicaltrials.gov (NCT01885013)；欧洲临床试验数据库（edract No.2009-014,662-26）。
Purpose To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. Methods CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. Results Seventy-two out of 126 randomized patients were evaluated: 57% had >= 1 IGF-1R positive CTC and 37.5% >= 4 IGF-1R negative cells; 42% had CTC count >= 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. Conclusion Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. Clinical trial registration: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).