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

  • Epidemiology
  • Published:
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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.

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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).

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    Authors and Affiliations

    1. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

      Chun Wang, Laura Austin, Zhong Ye, Carl Sun, Maysa Abu-Khalaf, Ronald E. Myers, Zhu Zhu, Yanna Ba & Hushan Yang

    2. Division of Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

      Zhaomei Mu, Giovanna Rossi & Massimo Cristofanilli

    3. Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, 19107, USA

      Inna Chervoneva

    4. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

      Juan P. Palazzo

    5. Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA

      Bingshan Li

    6. Robert H Lurie Comprehensive Cancer Center, Division of Hematology & Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

      Lifang Hou

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    1. Chun Wang
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    Correspondence to Massimo Cristofanilli or Hushan Yang.

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    Chun Wang and Zhaomei Mu contributed equally to this study.

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    Wang, C., Mu, Z., Chervoneva, I. et al. Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer. Breast Cancer Res Treat 161, 83–94 (2017). https://doi.org/10.1007/s10549-016-4026-2

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