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Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

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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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References

  1. Ministry of Health Law: Vital statistics of Japan; 2008. Available from http://www.mhlw.go.jp/english/database/db-hw/vs01.html

  2. Jemal A, Siegel R, Ward E et al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  3. Bartsch R, Wenzel C, Pluschnig U et al (2006) Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment. BMC Cancer 6:81

    Article  PubMed  Google Scholar 

  4. Cheung KL, Graves CR, Robertson JF (2000) Tumour marker measurements in the diagnosis and monitoring of breast cancer. Cancer Treat Rev 26:91–102

    Article  PubMed  CAS  Google Scholar 

  5. Duffy MJ (2005) Serum tumor markers in breast cancer: are they of clinical value? Clin Chem 52:345–351

    Article  Google Scholar 

  6. Khatcheressian JL, Wolff AC, Smith TJ et al (2006) American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24:5091–5097

    Article  PubMed  Google Scholar 

  7. Kurebayashi J, Nishimura R, Tanaka K et al (2004) Significance of serum tumor markers in monitoring advanced breast cancer patients treated with systemic therapy: a prospective study. Breast Cancer 11:389–395

    Article  PubMed  Google Scholar 

  8. Tampellini M, Berruti A, Bitossi R et al (2006) Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients. Breast Cancer Res Treat 98:241–248

    Article  PubMed  CAS  Google Scholar 

  9. Tondini C, Hayes DF, Gelman R et al (1988) Comparison of CA15-3 and carcinoembryonic antigen in monitoring the clinical course of patients with metastatic breast cancer. Cancer Res 48:4107–4112

    PubMed  CAS  Google Scholar 

  10. Cristofanilli M, Broglio KR, Guarneri V et al (2007) Circulating tumor cells in metastatic breast cancer: biologic staging beyond tumor burden. Clin Breast Cancer 7:471–479

    Article  PubMed  Google Scholar 

  11. Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791

    Article  PubMed  CAS  Google Scholar 

  12. Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430

    Article  PubMed  Google Scholar 

  13. Hayes DF, Cristofanilli M, Budd GT et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12:4218–4224

    Article  PubMed  CAS  Google Scholar 

  14. Nakamura S, Yagata H, Ohno S et al (2010) Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer. Breast Cancer 17:199–204

    Article  PubMed  Google Scholar 

  15. Yagata H, Nakamura S, Toi M et al (2008) Evaluation of circulating tumor cells in patients with breast cancer: multi-institutional clinical trial in Japan. Int J Clin Oncol 13:252–256

    Article  PubMed  Google Scholar 

  16. Apostolaki S, Perraki M, Pallis A et al (2007) Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance. Ann Oncol 18:851–858

    Article  PubMed  CAS  Google Scholar 

  17. Fehm T, Becker S, Duerr-Stoerzer S et al (2007) Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status. Breast Cancer Res 9:R74

    Article  PubMed  Google Scholar 

  18. Meng S, Tripathy D, Shete S et al (2004) HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA 101:9393–9398

    Article  PubMed  CAS  Google Scholar 

  19. Wulfing P, Borchard J, Buerger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 12:1715–1720

    Article  PubMed  Google Scholar 

  20. Pestrin M, Bessi S, Galardi F et al (2009) Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res Treat 118:523–530

    Article  PubMed  CAS  Google Scholar 

  21. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  22. Shimada M, Imura J, Kozaki T et al (2005) Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization. Oncol Rep 13:633–641

    PubMed  CAS  Google Scholar 

  23. Apostolaki S, Perraki M, Kallergi G et al (2009) Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance. Breast Cancer Res Treat 117:525–534

    Article  PubMed  Google Scholar 

  24. Fehm T, Hoffmann O, Aktas B et al (2009) Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res 11:R59

    Article  PubMed  Google Scholar 

  25. Ignatiadis M, Kallergi G, Ntoulia M et al (2008) Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res 14:2593–2600

    Article  PubMed  CAS  Google Scholar 

  26. Riethdorf S, Muller V, Zhang L et al (2010) Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the Neoadjuvant GeparQuattro Trial. Clin Cancer Res 16:2634–2645

    Article  PubMed  CAS  Google Scholar 

  27. Tewes M, Aktas B, Welt A et al (2009) Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat 115:581–590

    Article  PubMed  Google Scholar 

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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.

Author information

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 to Naoto 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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  • DOI: https://doi.org/10.1007/s10147-011-0260-0

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