通过联合监测基线循环肿瘤细胞和 DNA 对晚期乳腺癌患者进行风险分层和临床结局的早期评估。

Early Evaluation of Risk Stratification and Clinical Outcomes for Patients with Advanced Breast Cancer through Combined Monitoring of Baseline Circulating Tumor Cells and DNA.

机构信息

Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Circulating Tumor Cell (CTC) Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.

出版信息

Clin Cancer Res. 2024 Aug 15;30(16):3470-3480. doi: 10.1158/1078-0432.CCR-24-0535.

DOI:10.1158/1078-0432.CCR-24-0535

PMID:38829582

Abstract

PURPOSE

Early evaluation of tumor heterogeneity related to metastasis and outcomes is a major challenge in the management of advanced breast cancer (BCa) in the clinic. In this study, we introduced the value of baseline circulating tumor cells (CTC) and ctDNA for early differentiation of clinical stages, tumor heterogeneity, and prognosis in clinic.

EXPERIMENTAL DESIGN

A total of 292 patients with BCa were enrolled in this study, including 254 Stage IV and 38 Stage III patients, and examined the baseline levels of CTCs, CTC-clusters, and plasma ctDNA before initiating therapies. Outcomes including progression-free survival (PFS) and overall survival were evaluated using proportional hazards regression analysis.

RESULTS

The baseline CTCs, including HER2+ CTCs, in Stage IV patients were approximately 9.5 times higher than those detected in Stage III patients. Baseline CTC counts with a cutoff of 5 were significantly associated with the prognosis. Within each stage, patients with <5 CTCs had significantly longer PFS. Stage III patients with no CTCs exhibited the longest survival compared with patients with ≥1 CTC. CTC-clusters were only found in Stage IV patients, among whom 15 Stage IV patients with ≥5 CTC-clusters had the worst PFS compared with the 239 Stage IV patients with <5 CTC-clusters. Similar outcomes were observed in 28 out of 254 Stage IV patients who had at least one CTC-cluster detected, as these patients had shorter PFS compared with CTC-cluster negative group. The major differences in ctDNA mutations between patients with Stage III and Stage IV BCa were in PIK3CA and ESR1, which were associated with specific organ metastasis and worse outcomes.

CONCLUSIONS

Assessing the baseline levels of CTCs, CTC-clusters, and mutational ctDNA profile could reliably aid in differentiation of clinical stage and early prediction of metastasis and outcomes in advanced BCa.

摘要

目的

早期评估与转移和预后相关的肿瘤异质性是临床治疗晚期乳腺癌（BCa）的主要挑战。在本研究中，我们引入了基线循环肿瘤细胞（CTC）和 ctDNA 的价值，用于早期区分临床分期、肿瘤异质性和预后。

实验设计

共纳入 292 例 BCa 患者，包括 254 例 IV 期和 38 例 III 期患者，在开始治疗前检测基线 CTCs、CTC 簇和血浆 ctDNA 水平。使用比例风险回归分析评估无进展生存期（PFS）和总生存期等结局。

结果

IV 期患者的基线 CTCs，包括 HER2+ CTCs，约为 III 期患者的 9.5 倍。CTC 计数的截断值为 5 与预后显著相关。在每个分期内，CTC<5 的患者 PFS 显著延长。与 CTC≥1 的患者相比，无 CTC 的 III 期患者生存时间最长。CTC 簇仅在 IV 期患者中发现，其中 15 例 CTC 簇≥5 的 IV 期患者的 PFS 最差，与 239 例 CTC 簇<5 的 IV 期患者相比。在 254 例至少检测到一个 CTC 簇的 IV 期患者中也观察到了类似的结果，这些患者的 PFS 短于 CTC 簇阴性组。III 期和 IV 期 BCa 患者之间 ctDNA 突变的主要差异在于 PIK3CA 和 ESR1，这些突变与特定器官转移和不良结局相关。