학술논문
Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA.
Document Type
Article
Author
Ye, Zhong; Wang, Chun; Wan, Shaogui; Mu, Zhaomei; Zhang, Zhenchao; Abu-Khalaf, Maysa M.; Fellin, Frederick M.; Silver, Daniel P.; Neupane, Manish; Jaslow, Rebecca J.; Bhattacharya, Saveri; Tsangaris, Theodore N.; Chervoneva, Inna; Berger, Adam; Austin, Laura; Palazzo, Juan P.; Myers, Ronald E.; Pancholy, Neha; Toorkey, Darayus; Yao, Kaelan
Source
Subject
*BREAST cancer prognosis
*BREAST tumor treatment
*BIOPSY
*BLOOD collection
*CANCER patients
*EXTRACELLULAR space
*FLUORIMETER
*LONGITUDINAL method
*METASTASIS
*NUCLEIC acids
*POLYMERASE chain reaction
*TUMOR markers
*TREATMENT effectiveness
*PROPORTIONAL hazards models
*DISEASE progression
MORTALITY risk factors
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Language
ISSN
0959-8049
Abstract
Abstract Background Both circulating tumour cell (CTC) and total circulating cell-free DNA (ccfDNA) predict cancer patient prognosis. However, no study has explored the prognostic value of the combined use of CTC and ccfDNA. We aimed to investigate individual and joint effects of CTC and ccfDNA on clinical outcomes of metastatic breast cancer (MBC) patients. Methods We collected 227 blood samples from 117 MBC patients. CTCs were enumerated using the CellSearch System. ccfDNAs were quantified by quantitative real-time polymerase chain reaction and Qubit fluorometer. The individual and joint effects of CTC and ccfDNA levels on patient progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models. Results Compared to patients with <5 CTCs, patients with ≥5 CTCs had a 2.58-fold increased risk of progression and 3.63-fold increased risk of death. High level of ccfDNA was associated with a 2.05-fold increased risk of progression and 3.56-fold increased risk of death. These associations remained significant after adjusting for other important clinical covariates and CTC/ccfDNA levels. CTC and ccfDNA levels had a joint effect on patient outcomes. Compared to patients with low levels of both CTC and ccfDNA, those with high levels of both markers exhibited a >17-fold increased death risk (P < 0.001). Moreover, longitudinal analysis of 132 samples from 22 patients suggested that the inconsistency between CTC level and outcome in some patients could possibly be explained by ccfDNA level. Conclusions CTC and total ccfDNA levels were individually and jointly associated with PFS and OS in MBC patients. Highlights • Circulating tumour cell (CTC) or cell-free DNA (ccfDNA) associated with metastatic breast cancer (MBC) patient survivals. • Prognostic values of CTC and ccfDNA largely non-overlapping. • CTC and ccfDNA jointly associated with patient survival, especially overall survival. • Potential combined use of CTC and ccfDNA as liquid biopsy in MBC management. [ABSTRACT FROM AUTHOR]