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Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer

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Abstract

Background

Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3.

Methods

We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios.

Results

With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p < 0.0001). Seventy-one patients (72.4 %) had TM data at the time of CTC testing. To study the relationship between CTCs and TMs, we divided patients into normal TM and high TM groups. In the normal TM group, the CTC-negative patients had statistically significant survival than the CTC-positive patients (p = 0.005). The data suggested that CTC count could provide additional prognostic information beyond TMs for advanced/metastatic breast cancer. In multivariate analysis, the only significant predictor of overall survival was CTC ≥ 1 (hazard ratio, 3.026; 95 % confidence interval 1.350–6.784).

Conclusion

We found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (21591680) in Japan.

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Aichi Medical University, 1-1Yazakokarimata, Nagakute-city, Aichi Prefecture, 4801195, Japan

    Yukako Shiomi-Mouri, Junko Kousaka, Takahito Ando, Rie Tetsuka, Shogo Nakano, Miwa Yoshida, Kimihito Fujii, Miwa Akizuki, Tsuneo Imai & Takashi Fukutomi

  2. Department of Surgery, Sakura General Hospital, Niwa, Aichi, Japan

    Katsumasa Kobayashi

Authors
  1. Yukako Shiomi-Mouri
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  2. Junko Kousaka
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  3. Takahito Ando
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  4. Rie Tetsuka
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  5. Shogo Nakano
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  6. Miwa Yoshida
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  8. Miwa Akizuki
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  10. Takashi Fukutomi
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  11. Katsumasa Kobayashi
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Corresponding author

Correspondence to Shogo Nakano.

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Cite this article

Shiomi-Mouri, Y., Kousaka, J., Ando, T. et al. Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer. Breast Cancer 23, 120–127 (2016). https://doi.org/10.1007/s12282-014-0539-x

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  • DOI: https://doi.org/10.1007/s12282-014-0539-x

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