Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer (original) (raw)

Abstract

Backgrounds

The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known.

Methods

We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3–4 weeks later (first follow-up) were determined.

Results

The median follow-up time of the 52 enrolled patients was 655.0 days (18–1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival.

Conclusions

We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

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Acknowledgments

The authors thank Sachiko Ohde for statistical assistance; Bibari Nakamura, Keiko Shimizu, and all the staff from the Department of Breast Surgical Oncology, St. Luke’s International Hospital, for help in collecting clinical data; Masayuki Shimada, Takeshi Watanabe, and Yuki Matsuo from SRL Inc. for tissue analysis; and Sunita Patterson, Department of Scientific Publications, MD Anderson Cancer Center, for editorial review. This research is supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant, CA016672.

Conflict of interest

Yuji Shimoda is employed by SRL Inc., and SRL Inc. provided analysis of serum HER2 level in the blood samples at St. Luke’s International Hospital (Hayashi N, Nakamura S, Yoshida A, and Yagata H). All other coauthors have no conflict of interest.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 1354, Houston, TX, 77030, USA
    Naoki Hayashi, Gabriel N. Hortobagyi & Naoto T. Ueno
  2. Department of Breast Surgical Oncology, St. Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan
    Naoki Hayashi, Seigo Nakamura, Hiroshi Yagata & Atsushi Yoshida
  3. Second Department of Pathology, The Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
    Naoki Hayashi & Hidekazu Ota
  4. Department of Breast Surgical Oncology, The Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
    Seigo Nakamura
  5. Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
    Yasuharu Tokuda
  6. Research and Development Department, SRL Inc., 5-6-50 Shin-machi, Hino, Tokyo, 191-0002, Japan
    Yuji Shimoda
  7. Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA
    Massimo Cristofanilli

Authors

  1. Naoki Hayashi
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  2. Seigo Nakamura
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  3. Yasuharu Tokuda
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  4. Yuji Shimoda
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  5. Hiroshi Yagata
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  6. Atsushi Yoshida
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  7. Hidekazu Ota
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  8. Gabriel N. Hortobagyi
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  9. Massimo Cristofanilli
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  10. Naoto T. Ueno
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Corresponding author

Correspondence toNaoto T. Ueno.

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Hayashi, N., Nakamura, S., Tokuda, Y. et al. Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer.Int J Clin Oncol 17, 96–104 (2012). https://doi.org/10.1007/s10147-011-0260-0

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