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High-level expression of CXCR4 in breast cancer is associated with early distant and bone metastases

  • Research Article
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Tumor Biology

Abstract

Metastasis is the most life-threatening complication in all cancers. The chemokine receptor 4 (CXCR4) is expressed at high levels in many breast-cancer tumors and may modulate metastasis. We compared the time-to-metastasis and the sites of metastasis between breast-cancer tumors expressing CXCR4 at high or low levels. We enrolled 191 early breast cancer patients in our study. The expression of CXCR4 was evaluated using immunohistochemical staining, and the patients were divided into low-level (CXCR4−) and high-level (CXCR4+) CXCR4 expression groups. Associations between the patients’ level of CXCR4 expression and their basic clinical characteristics, time-to-metastasis, and metastatic sites were examined using a Cox proportional-hazards regression model. A total of 107 CXCR4+ patients (56 %) were identified. No statistical differences were evident in basic characteristics between the CXCR4+ and CXCR4− groups. The CXCR4+ group had a higher incidence of distant metastasis during the first year (10.3 % versus 1.1 %, P = 0.009) and shorter event-free survival (17.43 months versus 27.5 months, P = 0.026) than those of the CXCR4− group. The CXCR4+ group also had a higher incidence of bone metastasis (P = 0.008) than the CXCR4− group. No significant difference in metastasis sites in other organs was observed between the two groups. A high level of CXCR4 expression in breast cancer is associated with early distant and bone metastases. The CXCR4+ phenotype may be a useful predictor for the prevention of early treatment failure and bone metastasis in breast cancer patients. This retrospective study shows that a high expression of CXCR4 in breast cancer is associated with earlier distant metastasis and bone metastasis in breast cancer.

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Abbreviations

CXCR4:

Chemokine receptor 4

SDF-1:

Stromal-derived factor-1, also known as CXCL12

ER:

Estrogen receptor

PR:

Progesterone receptor

Her-2:

Human epidermal growth factor receptor 2, also known as ErbB-2

FISH:

Fluorescent in situ hybridization

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Acknowledgments

This study was supported by grants from Taipei Medical University/Taipei Medical University Hospital (102TMU-TMUH-09), and the National Science Council, Taiwan (NSC 100-2632-B-038-001-MY3). Support for the statistical analysis was provided by the Center of Excellence for Clinical Trials and Research in Neuroscience (DOH99-TD-B-111-003).

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Authors and Affiliations

  1. Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China

    Chin-Sheng Hung, Hung-Hwa Liang, Chih-Hsiung Wu, Po-Li Wei & Yu-Jia Chang

  2. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China

    Chin-Sheng Hung, Hung-Hwa Liang, Chih-Hsiung Wu, Po-Li Wei & Yu-Jia Chang

  3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250, Wu-Xing Street, Taipei, Taiwan, Republic of China

    Hung-Hwa Liang, Chih-Hsiung Wu & Yu-Jia Chang

  4. Department of Surgery, Saint Mary’s Hospital Luodong, Yilan County, Taiwan

    Hou-Yu Su

  5. Division of General Surgery, Departments of Surgery, Buddhist Tzu-Chi General Hospital Taipei Branch, Taipei, Taiwan, Republic of China

    Chieh-Wen Lai

  6. Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, Republic of China

    Yo-Cheng Chang

  7. Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan, Republic of China

    Yuan-Soon Ho & Yu-Jia Chang

  8. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei, Republic of China

    Yuan-Soon Ho

  9. Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China

    Yuan-Soon Ho

  10. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China

    Chih-Hsiung Wu

  11. Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China

    Jau-De Ho

  12. Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China

    Po-Li Wei & Yu-Jia Chang

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  1. Chin-Sheng Hung
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  2. Hou-Yu Su
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  3. Hung-Hwa Liang
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  4. Chieh-Wen Lai
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  5. Yo-Cheng Chang
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  6. Yuan-Soon Ho
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  7. Chih-Hsiung Wu
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  8. Jau-De Ho
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  9. Po-Li Wei
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  10. Yu-Jia Chang
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Correspondence to Po-Li Wei or Yu-Jia Chang.

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Hung, CS., Su, HY., Liang, HH. et al. High-level expression of CXCR4 in breast cancer is associated with early distant and bone metastases. Tumor Biol. 35, 1581–1588 (2014). https://doi.org/10.1007/s13277-013-1218-9

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  • DOI: https://doi.org/10.1007/s13277-013-1218-9

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