海报库PosterKeep
PO.CL01.22 · 临床研究

治疗前循环肿瘤细胞是接受abemaciclib治疗的转移性乳腺癌患者进展的重要预测因子

Pre-treatment circulating tumor cells are a significant predictor of progression in patients with metastatic breast cancer undergoing abemaciclib therapy

编号 1074 展板 14 时间 4/19 02:00–05:00 区域 Section 42 主讲 Qiang Zhang, MD;PhD
分会场 Circulating Tumor Cells, Metastasis, and Dissemination Biology 1
该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Qiang Zhang1, Justin Zhang2, Andrew A. Davis3, Natalie Heater4, Diana Jaber5, Paolo D’Amico6, Jianhua Jiao7, Weijun Qin8, Pan Du9, Shading Jia9, Akhil Chawla10, Janice Lu11, Lisa Flaum4, William J. Gradishar1

1Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Cancer Center, Northwestern University - Evanston, Chicago, IL,2Department of Surgery, Division of Surgical Oncology, Northwestern University and Whitney High School, Chicago, IL,3Washington University School of Medicine in St. Louis, St. Louis, MO,4Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL,5Department of Medicine, Division of Hematology and Oncology, Northwestern University, Chicago, IL,6Northwestern University, Chicago, IL,7Fourth Military Medical University, Xi‘an, China,8Department of Urology, Fourth Military Medical University, Xi‘an, China,9Predicine Inc, San Francisco, CA,10Department of Surgery, Division of Surgical Oncology, Northwestern University, Chicago, IL,11Department of Medicine, Division of Hematology and Oncology, Stanford University, Stanford, CA

摘要 Abstract

中文摘要
背景：Abemaciclib是一种广泛用于治疗转移性乳腺癌(MBC)的CDK4/6抑制剂，已显著改善无进展生存期。然而，尽管有这些治疗获益，仍有相当比例的患者会经历复发。这一持续存在的临床挑战凸显了对能在治疗开始前识别高危个体的可靠生物标志物的迫切需求，而这方面的探索仍不充分。我们此前的工作表明，监测循环肿瘤细胞(CTCs)及ctDNA突变可作为预测MBC不良预后的工具(ASCO 2025 #1042；AACR 2025 #3613；CCR 2024)。此处，我们报告新的发现，证明基线CTC水平对识别接受abemaciclib患者的复发风险具有重要预测价值。 方法：共纳入66例ER+/HER2−的MBC患者，由于部分个体治疗中断及再启动，在西北纪念医院(2016-2024年，IRB：NU16B06)共实施了76个疗程的abemaciclib治疗。中位随访期为36.3个月。在患者启动abemaciclib治疗前采集血液样本(7.5 mL)。CTC计数(分类为CK+/DAPI+/CD45−)在FDA批准的CELLTRACKS系统中进行。使用集成学习方法的因果推断进行统计分析。 结果：在76个疗程中，28例患者CTC计数≥5，48例患者CTC计数<5。根据abemaciclib治疗后的进展情况，将所有患者分为两个队列。第一项分析(截止值：6个月)：队列1(早期进展<6个月)：29例患者(范围：0.5-5.5个月；中位数：2.75个月)；队列2(晚期进展≥6个月)：36例患者(范围：6.5-45个月；中位数：17.5个月)，另加研究结束时无进展的11例患者(随访：>12至>70个月)。队列1的平均CTC计数为9.2，显著高于队列2的6.1(P<0.01)。第二项分析(截止值：12个月)：队列1(早期进展<12个月)：41例患者(范围：0.5-11个月；中位数：3.75个月)。队列2(晚期进展≥12个月)：24例患者，另加同样的11例无进展患者。队列1的平均CTC计数为11.2，显著高于队列2的2.8(P<0.01)。晚期进展组(平均2.3)与无进展组(平均3.1)之间CTC水平无显著差异。 结论：这些发现首次证明，治疗前CTC水平可作为abemaciclib治疗后进展的强预测因子。因此，早期识别MBC患者升高的CTCs对于优化CDK4/6抑制剂治疗策略及识别可能受益于替代治疗方法的患者可能至关重要。
查看英文原文 English abstract
Background: Abemaciclib, a CDK4/6 inhibitor widely used in the treatment of metastatic breast cancer (MBC), has significantly improved progression-free survival. However, despite these therapeutic benefits, a substantial proportion of patients still experience recurrence. This ongoing clinical challenge highlights the urgent need for reliable biomarkers that can identify high-risk individuals before treatment initiation which remains insufficiently explored. Our previous work showed that monitoring circulating tumor cells (CTCs) and ctDNA mutations can serve as a predictive tool for poor prognosis in MBC (ASCO 2025 #1042; AACR 2025 #3613; CCR 2024). Here, we report new findings demonstrating that baseline CTC levels provide important predictive value for identifying recurrence risk in patients receiving abemaciclib. Methods: A total of 66 ER + /HER2 − MBC patients were enrolled, and due to treatment discontinuation and re-initiation among some individuals, 76 courses of abemaciclib therapy were administered at Northwestern Memorial Hospital (2016-2024, IRB: NU16B06). The median follow-up period was 36.3 months. Blood samples (7.5 mL) were collected from patients prior to initiating abemaciclib therapy. CTC enumeration (classified as CK+/DAPI+/CD45−) was performed in FDA-approved CELLTRACKS System. Statistical analyses were conducted using causal inference with ensemble learning approaches. Results: Of the 76 treatment courses, 28 patients had CTC counts ≥5, while 48 patients had CTC counts <5. All patients were categorized into two cohorts based on progression after abemaciclib treatment. First analysis (cut-off: 6 months): Cohort 1 (early progression <6 months): 29 patients (range: 0.5-5.5 months; median: 2.75 months); Cohort 2 (late progression ≥6 months): 36 patients (range: 6.5-45 months; median: 17.5 months), plus 11 patients with no progression at the end of the study (follow-up: >12 to >70 months). The mean CTC count in Cohort 1 was 9.2, significantly higher than 6.1 in Cohort 2 (P < 0.01). Second analysis (cut-off: 12 months): Cohort 1 (early progression <12 months): 41 patients (range: 0.5-11 months; median: 3.75 months). Cohort 2 (late progression ≥12 months): 24 patients, plus the same 11 patients with no progress. The mean CTC count in Cohort 1 was 11.2, significantly higher than 2.8 in Cohort 2 (P < 0.01). There was no significant difference in CTC levels between the late-progression group (mean 2.3) and the no-progression group (mean 3.1). Conclusions: These findings demonstrate, for the first time, that pre-treatment CTC levels serve as a strong predictor of progress following abemaciclib therapy. Early identification of elevated CTCs in patients with MBC may therefore be critical for optimizing CDK4/6 inhibitor treatment strategies and identifying patients who may benefit from alternative therapeutic approaches.
利益披露 Disclosure
Q. Zhang, None.. J. Zhang, None.. N. Heater, None.. D. Jaber, None.. P. D’Amico, None.. J. Jiao, None.. W. Qin, None.. P. Du, None.. S. Jia, None.. A. Chawla, None.. J. Lu, None.. L. Flaum, None.. W. J. Gradishar, None.

← 返回 AACR 2026 检索