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

Qiang Zhang*, Zheng Cai, Lorenzo Gerratana, Andrew A. Davis, Paolo D’Amico, Akhil Chawla, Saya Jacob, Youbin Zhang, Jianhua Jiao, Weijun Qin, Carolina Reduzzi, Lisa Flaum, Ami N Shah, William J Gradishar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3470-3480
Number of pages11
JournalClinical Cancer Research
Volume30
Issue number16
DOIs
StatePublished - Aug 15 2024

Funding

The authors thank Drs. Shidong Jia and Pan Du from Predicine Inc. as consultants on ctDNA technique with this report. This study was supported in part by grants from the Lynn Sage Breast Cancer Research OncoSET Program at the Robert H. Lurie Cancer Center, Northwestern University, and in part by the National Natural Science Foundation of China (No. 82220108004). L. Gerratana reports personal fees from Menarini Stemline, AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Merck Sharp & Dohme, and Pfizer, as well as grants from Menarini Silicon Biosystems outside the submitted work. A.A. Davis reports personal fees from Pfizer and Biotheranostics, as well as grants from Breast Cancer Alliance outside the submitted work. P. D\u2019Amico reports personal fees from Merck & Co. outside the submitted work. L. Flaum reports personal fees from AstraZeneca and Novartis outside the submitted work. A. Shah reports personal fees from Gilead, AstraZeneca, Lilly, and Novartis outside the submitted work. No disclosures were reported by the other authors.

ASJC Scopus subject areas

  • General Medicine

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