转移性乳腺癌患者参与 DETECT 研究项目时循环肿瘤细胞 HER2 状态的预后相关性。
Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program.
机构信息
Department of Gynecology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Gynecology and Obstetrics Department, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Medical Faculty, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
出版信息
ESMO Open. 2021 Dec;6(6):100299. doi: 10.1016/j.esmoop.2021.100299. Epub 2021 Nov 25.
BACKGROUND
Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors.
PATIENTS AND METHODS
Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining).
RESULTS
Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS.
CONCLUSION
CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.
背景
循环肿瘤细胞（CTCs）已被报道可预测转移性乳腺癌（MBC）的临床结局。CTCs 的生物学特性可能与原发肿瘤不同，并且在一些 HER2 阴性肿瘤患者中也存在 HER2 阳性 CTCs。
患者和方法
在开始新的治疗线之前，对 HER2 阴性 MBC 患者进行了 DETECT III 和 IV 试验的参与筛选。使用 CELLSEARCH 分析血液样本。用抗 HER2 抗体标记 CTCs，并根据染色强度（阴性、弱阳性、中度阳性或强阳性）进行分类。
结果
对 1933 例 HER2 阴性 MBC 患者的筛选血样进行了分析。在 1933 例筛选患者中，多达 1217 例（63.0%）每 7.5ml 血液中存在≥1 个 CTC；735 例（38.0%；范围 1-35078 CTCs，中位数 8 CTCs）检测到≥5 个 CTCs。在 1159 例 CTC 阳性患者中评估了 CTCs 的 HER2 状态；在 174 例（15.0%）患者中发现≥1 个 CTC 具有强 HER2 染色。单个患者的所有 CTC 中具有强 HER2 染色的 CTCs 比例在 0.06%至 100%之间（平均值为 15.8%）。雌激素受体（ER）和孕激素受体（PR）阳性肿瘤的患者更有可能存在≥1 个具有强 HER2 染色的 CTC。CTC 状态与总生存期（OS）显著相关。检测到≥1 个具有强 HER2 染色的 CTC 与较短的 OS 相关[仅在具有阴性至中度 HER2 染色的 CTCs 的患者中，9.7（7.1-12.3）与 16.5（14.9-18.1）个月，P=0.013]。在多变量分析中，年龄、ER 状态、PR 状态、东部合作肿瘤学组表现状态、治疗线和 CTC 状态独立预测 OS。
结论
在 HER2 阴性疾病患者中检测 CTCs 是一个强有力的预后因素。存在≥1 个具有强 HER2 染色的 CTC 与较短的 OS 相关，支持 CTCs 上 HER2 表达的生物学作用。
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