Detection and HER2 Expression of Circulating Tumor Cells: Prospective Monitoring in Breast Cancer Patients Treated in the Neoadjuvant GeparQuattro Trial
Detection and HER2 Expression of Circulating Tumor Cells: Prospective Monitoring in Breast Cancer Patients Treated in the Neoadjuvant GeparQuattro Trial
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DOI：
10.1158/1078-0432.ccr-09-2042
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发表时间：
2010-05-01
影响因子：
11.5
通讯作者：
Pantel, Klaus
中科院分区：
文献类型：
--
作者：
Riethdorf, Sabine;Mueller, Volkmar;Pantel, Klaus
目的：本研究旨在检测和表征乳腺癌患者外周血新辅助治疗 (NT) 之前和之后的循环肿瘤细胞 (CTC)。 实验设计：GeparQuattro 临床试验纳入 NT 方法（表阿霉素/环磷酰胺随机分配至单用多西他赛、多西他赛联合卡培他滨或多西他赛） 其次是卡培他滨）和针对 HER2 阳性肿瘤患者的额外曲妥珠单抗治疗。我们使用食品和药物管理局批准的 CellSearch 系统进行 CTC 检测和 HER2 表达评估，并开发了 CTC 的 HER2 免疫评分。结果：我们在 NT 前 213 名患者中的 46 名 (21.6%) 中检测到 >= 1 CTC/7.5 mL，在 NT 后 207 名患者中 22 名 (10.6%) 中检测到 >= 1 CTC/7.5 mL (P = 0.002)。 20 例（15.0%）最初 CTC 阳性的病例在 NT 后呈 CTC 阴性，而 11 例（8.3%）在 NT 后呈 CTC 阳性，尽管在 NT 前未发现 CTC。 CTC 检测与原发肿瘤特征无关。此外，肿瘤对 NT 的反应与 CTC 检测之间没有关联。 58 名 CTC 阳性患者中有 14 名 (24.1%) 观察到 HER2 过表达 CTC，其中包括 8 名 HER2 阴性原发肿瘤患者和 3 名接受曲妥珠单抗治疗后的患者。在 21 名 HER2 阳性原发肿瘤患者中，有 11 名患者在 NT 之前或之后 CTC 评分为 HER2 阴性或弱 HER2 阳性。 CTC 上 HER2 过表达仅限于导管癌，且与高肿瘤分期相关（P = 0.002）。结论：原发性乳腺癌患者中 CTC 数量较低。治疗期间 CTC 发生率的下降与标准临床特征和原发肿瘤反应不相关。有关 CTC HER2 状态的信息可能有助于针对 HER2 的治疗进行分层和监测。临床癌症研究； 16（9）； 2634-45。 (C) 2010 AACR。
Purpose: This study was aimed at detecting and characterizing circulating tumor cells (CTC) before and after neoadjuvant therapy (NT) in the peripheral blood of patients with breast cancer.Experimental Design: The clinical trial GeparQuattro incorporated NT approaches (epirubicin/cyclophosphamide prior to randomization to docetaxel alone, docetaxel in combination with capecitabine, or docetaxel followed by capecitabine) and additional trastuzumab treatment for patients with HER2-positive tumors. We used the Food and Drug Administration-approved CellSearch system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC.Results: We detected >= 1 CTC/7.5 mL in 46 of 213 patients (21.6%) before NT and in 22 of 207 patients (10.6%) after NT (P = 0.002). Twenty (15.0%) initially CTC-positive cases were CTC-negative after NT, whereas 11 (8.3%) cases were CTC-positive after NT, although no CTC could be found before NT. CTC detection did not correlate with primary tumor characteristics. Furthermore, there was no association between tumor response to NT and CTC detection. HER2-overexpressing CTC were observed in 14 of 58 CTC-positive patients (24.1%), including 8 patients with HER2-negative primary tumors and 3 patients after trastuzumab treatment. CTC scored HER2-negative or weakly HER2-positive before or after NT were present in 11 of 21 patients with HER2-positive primary tumors. HER2 overexpression on CTC was restricted to ductal carcinomas and associated with high tumor stage (P = 0.002).Conclusion: CTC number was low in patients with primary breast cancer. The decrease in CTC incidence during treatment was not correlated with standard clinical characteristics and primary tumor response. Information on the HER2 status of CTC might be helpful for stratification and monitoring of HER2-directed therapies. Clin Cancer Res; 16(9); 2634-45. (C) 2010 AACR.