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Breast Cancer Research and Treatment

, Volume 161, Issue 1, pp 83–94 | Cite as

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 CristofanilliEmail author
  • Hushan YangEmail author
Epidemiology

Abstract

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.

Keywords

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

Notes

Acknowledgments

This study is supported by Thomas Jefferson University Cancer Center Support Grant (5P30CA056036-17) for the CTC Core Facility, Pennsylvania Department of Health Grant (SAP# 4100062221), The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund, and American Cancer Society Research Scholar Grant (123741-RSG-13-003-01-CCE).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2016_4026_MOESM1_ESM.docx (28 kb)
Supplementary material 1 (DOCX 27 kb)
10549_2016_4026_MOESM2_ESM.pptx (65 kb)
Supplementary material 2 (PPTX 65 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Chun Wang
    • 1
  • Zhaomei Mu
    • 2
  • Inna Chervoneva
    • 3
  • Laura Austin
    • 1
  • Zhong Ye
    • 1
  • Giovanna Rossi
    • 2
  • Juan P. Palazzo
    • 4
  • Carl Sun
    • 1
  • Maysa Abu-Khalaf
    • 1
  • Ronald E. Myers
    • 1
  • Zhu Zhu
    • 1
  • Yanna Ba
    • 1
  • Bingshan Li
    • 5
  • Lifang Hou
    • 6
  • Massimo Cristofanilli
    • 2
    Email author
  • Hushan Yang
    • 1
    Email author
  1. 1.Department of Medical Oncology, Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Division of Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Department of Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  3. 3.Department of Pharmacology and Experimental TherapeuticsThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Department of PathologyThomas Jefferson UniversityPhiladelphiaUSA
  5. 5.Center for Human Genetics Research, Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA
  6. 6.Robert H Lurie Comprehensive Cancer Center, Division of Hematology & Oncology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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