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Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer

  • Epidemiology
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Abstract

The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch® system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients’ progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57–4.86, P log-rank = 0.0005] and 2.83 (1.48–5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02–4.78) and 3.32 (1.68–6.55), respectively (P log-rank = 0.0006, P trend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.

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Acknowledgments

The work reported in this study received supports from Thomas Jefferson University, 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

      Zhaomei Mu, Chun Wang, Zhong Ye, Laura Austin, Rebecca Jaslow, Ronald E. Myers, Juntao Jiang, Hushan Yang & Massimo Cristofanilli

    2. Department of Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA

      Jesse Civan

    3. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, 27710, USA

      Terry Hyslop

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

      Juan P. Palazzo

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

      Bingshan Li

    6. State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi’an, 710032, China

      Jinliang Xing

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    1. Zhaomei Mu
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    Correspondence to Hushan Yang or Massimo Cristofanilli.

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    Zhaomei Mu and Chun Wang have contributed equally to this work.

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    Mu, Z., Wang, C., Ye, Z. et al. Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer. Breast Cancer Res Treat 154, 563–571 (2015). https://doi.org/10.1007/s10549-015-3636-4

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    • DOI: https://doi.org/10.1007/s10549-015-3636-4

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