Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer

Chun Wang, Zhaomei Mu, Inna Chervoneva, Laura Austin, Zhong Ye, Giovanna Rossi, Juan P. Palazzo, Carl Sun, Maysa Abu-Khalaf, Ronald E. Myers, Zhu Zhu, Yanna Ba, Bingshan Li, Lifang Hou, Massimo Cristofanilli, Hushan Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Purpose: Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication. Methods: CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients. The associations between baseline, first follow-up, and longitudinal enumerations of CTCs and CTC-clusters with patient progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. Results: CTC and CTC-cluster counts at both baseline and first follow-up were significantly associated with patient PFS and OS. Time-dependent analysis of longitudinally collected samples confirmed the significantly unfavorable PFS and OS in patients with ≥5 CTCs, and further demonstrated the independent prognostic values by CTC-clusters compared to CTC-enumeration alone. Longitudinal analyses also identified a link between the size of CTC-clusters and patient OS: compared to the patients without any CTC, those with 2-cell CTC-clusters and ≥3-cell CTC-clusters had a hazard ratio (HR) of 7.96 [95 % confidence level (CI) 2.00–31.61, P = 0.003] and 14.50 (3.98–52.80, P < 0.001), respectively. Conclusions: In this novel time-dependent analysis of longitudinally collected CTCs and CTC-clusters, we showed that CTC-clusters added additional prognostic values to CTC enumeration alone, and a larger-size CTC-cluster conferred a higher risk of death in MBC patients.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalBreast Cancer Research and Treatment
Issue number1
StatePublished - Jan 1 2017


  • Circulating tumor cell clusters (CTC-clusters)
  • Circulating tumor cells (CTCs)
  • Metastatic breast cancer (MBC)
  • Prognosis
  • Time-dependent analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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