Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA

Zhong Ye, Chun Wang, Shaogui Wan, Zhaomei Mu, Zhenchao Zhang, Maysa M. Abu-Khalaf, Frederick M. Fellin, Daniel P. Silver, Manish Neupane, Rebecca J. Jaslow, Saveri Bhattacharya, Theodore N. Tsangaris, Inna Chervoneva, Adam Berger, Laura Austin, Juan P. Palazzo, Ronald E. Myers, Neha Pancholy, Darayus Toorkey, Kaelan YaoMax Krall, Xiuling Li, Xiaobing Chen, Xiuhong Fu, Jinliang Xing, Lifang Hou, Qiang Wei, Bingshan Li, Massimo Cristofanilli, Hushan Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalEuropean Journal of Cancer
StatePublished - Jan 2019


  • Circulating cell-free DNA (ccfDNA)
  • Circulating tumour cell (CTC)
  • Metastatic breast cancer (MBC)
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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