Tumor Biology

, Volume 35, Issue 2, pp 1581–1588 | Cite as

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

  • Chin-Sheng Hung
  • Hou-Yu Su
  • Hung-Hwa Liang
  • Chieh-Wen Lai
  • Yo-Cheng Chang
  • Yuan-Soon Ho
  • Chih-Hsiung Wu
  • Jau-De Ho
  • Po-Li Wei
  • Yu-Jia Chang
Research Article


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.


CXCR4 Metastasis Bone metastasis Breast neoplasm 



Chemokine receptor 4


Stromal-derived factor-1, also known as CXCL12


Estrogen receptor


Progesterone receptor


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


Fluorescent in situ hybridization



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).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Chin-Sheng Hung
    • 1
    • 2
  • Hou-Yu Su
    • 4
  • Hung-Hwa Liang
    • 1
    • 2
    • 3
  • Chieh-Wen Lai
    • 5
  • Yo-Cheng Chang
    • 6
  • Yuan-Soon Ho
    • 7
    • 8
    • 9
  • Chih-Hsiung Wu
    • 1
    • 2
    • 3
    • 10
  • Jau-De Ho
    • 11
  • Po-Li Wei
    • 1
    • 2
    • 12
  • Yu-Jia Chang
    • 1
    • 2
    • 3
    • 7
    • 12
  1. 1.Division of General Surgery, Department of SurgeryTaipei Medical University HospitalTaipeiRepublic of China
  2. 2.Department of SurgerySchool of Medicine, College of Medicine, Taipei Medical UniversityTaipeiRepublic of China
  3. 3.Graduate Institute of Clinical MedicineCollege of Medicine, Taipei Medical UniversityTaipeiRepublic of China
  4. 4.Department of SurgerySaint Mary’s Hospital LuodongYilan CountyTaiwan
  5. 5.Division of General Surgery, Departments of Surgery, Buddhist Tzu-Chi General Hospital Taipei BranchTaipeiRepublic of China
  6. 6.Graduate Institute of Biomedical InformaticsCollege of Medical Science and Technology, Taipei Medical UniversityTaipeiRepublic of China
  7. 7.Center of Excellence for Cancer ResearchTaipei Medical UniversityTaipeiRepublic of China
  8. 8.School of Medical Laboratory Science and Biotechnology, College of Medical Science and TechnologyTaipeiRepublic of China
  9. 9.Graduate Institute of Medical ScienceCollege of Medicine, Taipei Medical UniversityTaipeiRepublic of China
  10. 10.Division of General Surgery, Department of Surgery, Shuang Ho HospitalTaipei Medical UniversityTaipeiRepublic of China
  11. 11.Department of OphthalmologyTaipei Medical University HospitalTaipeiRepublic of China
  12. 12.Cancer Research CenterTaipei Medical University HospitalTaipeiRepublic of China

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