循环肿瘤细胞 HER2 表型对转移性乳腺癌的影响：107 例回顾性研究。
The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients.
机构信息
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße 7, 72076, Tübingen, Germany.
出版信息
BMC Cancer. 2015 May 14;15:403. doi: 10.1186/s12885-015-1423-6.
BACKGROUND
In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients. Reassessment of predictive markers, including human epidermal growth factor receptor 2 (HER2) expression, might help to optimize MBC treatment. While tissue sampling is invasive and often difficult to repeat, circulating tumor cell (CTC) analysis requires only a blood sample and might provide an easy-to-repeat, real-time "liquid biopsy" approach. The present retrospective study was conducted to compare HER2 expression in primary tumors, metastatic tissue, and circulating tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) in MBC.
METHODS
CTC-positive (five or more CTCs/7.5 mL blood; CellSearch®, Janssen Diagnostics) MBC patients starting a new line of systemic treatment were eligible for the study. HER2 status of CTCs was determined by immunofluorescence (CellSearch®). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue was determined by immunohistochemistry. Data were analyzed using descriptive statistics and Kaplan-Meier plots.
RESULTS
One hundred seven patients (median age (range) 57 (33-81) years) were included. 100/107 (93%) patients were followed-up for a median [95% confidence interval (CI)] of 28.5 [25.1-40.1] months. Of 37/107 (35%) CTC-HER2-positive patients only 10 (27%) were PRIM-HER2-positive. 6/46 (13%) patients were MET-HER2-positive; only 2/10 (20%) CTC-HER2-positive patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and PRIM-HER2 and MET-HER2 status was 69% and 74%, respectively. Kaplan-Meier plots of PFS and OS by CTC-HER2 status revealed significantly longer median [95% CI] PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7-13.7] versus 4.34 [3.5-5.9] months; p = 0.035). CTC-HER2-positive status showed no significant difference for OS (13.7 [7.7-30.0] versus 8.7 [5.9-15.3] months; p = 0.287).
CONCLUSIONS
HER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform "liquid biopsy" to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed.
背景
在转移性乳腺癌（MBC）中，多达 20%的患者转移组织和原发肿瘤的抗原谱不同。重新评估预测标志物，包括人表皮生长因子受体 2（HER2）表达，可能有助于优化 MBC 治疗。虽然组织采样具有侵袭性且往往难以重复，但循环肿瘤细胞（CTC）分析仅需要采集血液样本，并且可能提供一种易于重复的实时“液体活检”方法。本回顾性研究旨在比较 MBC 患者的原发肿瘤、转移性组织和循环肿瘤细胞（CTC）中的 HER2 表达，并分析 CTC 中 HER2 过表达对 MBC 无进展生存期（PFS）和总生存期（OS）的潜在影响。
方法
开始新的系统治疗线的 CTC 阳性（五个或更多 CTC/7.5 mL 血液；CellSearch®，Janssen Diagnostics）MBC 患者有资格参加这项研究。通过免疫荧光法（CellSearch®）确定 CTC 的 HER2 状态。通过免疫组织化学法确定原发（PRIM）和转移性（MET）肿瘤组织的 HER2 状态。使用描述性统计和 Kaplan-Meier 图进行数据分析。
结果
107 例患者（中位年龄（范围）57（33-81）岁）入选。100/107（93%）患者中位随访[95%置信区间（CI）]28.5 [25.1-40.1]个月。在 37/107（35%）CTC-HER2 阳性患者中，仅 10 例（27%）为 PRIM-HER2 阳性。6/46（13%）患者为 MET-HER2 阳性；仅 2/10（20%）CTC-HER2 阳性患者为 MET-HER2 阳性。CTC-HER2 表达与 PRIM-HER2 和 MET-HER2 状态之间的总准确性分别为 69%和 74%。根据 CTC-HER2 状态的 PFS 和 OS 的 Kaplan-Meier 图显示，CTC-HER2 阳性患者的中位 PFS 明显长于 CTC-HER2 阴性患者（7.4 [4.7-13.7]与 4.34 [3.5-5.9]个月；p = 0.035）。CTC-HER2 阳性状态对 OS 无显著差异（13.7 [7.7-30.0]与 8.7 [5.9-15.3]个月；p = 0.287）。
结论
HER2 状态在乳腺癌的病程中可能发生变化。CTC 表型分析可作为一种易于进行的“液体活检”方法，重新评估 HER2 状态并可能指导治疗决策。此外，还需要进行前瞻性研究。
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