TY - JOUR
T1 - Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA
AU - Ye, Zhong
AU - Wang, Chun
AU - Wan, Shaogui
AU - Mu, Zhaomei
AU - Zhang, Zhenchao
AU - Abu-Khalaf, Maysa M.
AU - Fellin, Frederick M.
AU - Silver, Daniel P.
AU - Neupane, Manish
AU - Jaslow, Rebecca J.
AU - Bhattacharya, Saveri
AU - Tsangaris, Theodore N.
AU - Chervoneva, Inna
AU - Berger, Adam
AU - Austin, Laura
AU - Palazzo, Juan P.
AU - Myers, Ronald E.
AU - Pancholy, Neha
AU - Toorkey, Darayus
AU - Yao, Kaelan
AU - Krall, Max
AU - Li, Xiuling
AU - Chen, Xiaobing
AU - Fu, Xiuhong
AU - Xing, Jinliang
AU - Hou, Lifang
AU - Wei, Qiang
AU - Li, Bingshan
AU - Cristofanilli, Massimo
AU - Yang, Hushan
N1 - Funding Information:
This work was supported by National Cancer Institute Grant ( CA207468 ), Thomas Jefferson University Cancer Center Support Grant ( 5P30CA056036-17 ) for the CTC Core Facility, Pennsylvania Department of Health Grant ( SAP# 4100062221 ) and Jamie Lieberman Memorial Endowment Trust . The funding agencies were not involved in the design, conduct, analysis or interpretation of the study.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Circulating cell-free DNA (ccfDNA)
KW - Circulating tumour cell (CTC)
KW - Metastatic breast cancer (MBC)
KW - Prognosis
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U2 - 10.1016/j.ejca.2018.10.012
DO - 10.1016/j.ejca.2018.10.012
M3 - Article
C2 - 30528798
AN - SCOPUS:85057878734
VL - 106
SP - 133
EP - 143
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -