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Annals of Oncology Advance Access originally published online on February 23, 2009
Annals of Oncology 2009 20(6):1013-1019; doi:10.1093/annonc/mdn740
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

Chemokine receptors in advanced breast cancer: differential expression in metastatic disease sites with diagnostic and therapeutic implications

N. Cabioglu1,{dagger}, A. A. Sahin1, P. Morandi2, F. Meric-Bernstam3, R. Islam2, H. Y. Lin4, C. D. Bucana5, A. M. Gonzalez-Angulo2, G. N. Hortobagyi2 and M. Cristofanilli2,*

1 Department of Pathology
2 Department of Breast Medical Oncology
3 Department of Surgical Oncology
4 Department of Bioistatistics and Applied Mathematics
5 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, USA

* Correspondence to: Dr M. Cristofanilli, Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, PO Box 301439, Houston, TX 77230, USA. Tel: +1-713-792-2817; Fax: +1-713-794-4385; E-mail: mcristof{at}mdanderson.org

Background: We investigated the expression of CXCR4, CCR7, estrogen receptor (ER), progesterone receptor (PR) and HER2-neu in human metastatic breast cancers to determine whether these biological biomarkers were preferentially expressed in any organ-specific metastases.

Materials and methods: CXCR4, CCR7, ER, PR and HER2-neu expression levels were evaluated by immunohistochemical staining using paraffin-embedded tissue sections of metastatic breast cancers (n = 41) obtained by either diagnostic biopsy or surgical resection.

Results: The metastatic sites included the following: bone (n = 15), brain (n = 14), lung (n = 6), liver (n = 2), and omental metastases (n = 2). CXCR4 was expressed in 41% of cases, CCR7 expression was demonstrated in 10%, and HER2-neu overexpression was present in 27%. CXCR4 was more likely to be expressed in bone metastases than visceral metastases (67% versus 26%, P = 0.020). Visceral sites demonstrated a lower rate of CXCR4 positivity (33% and 23%, respectively, for lung and brain metastases). Similarly, CCR7 was more likely to be found in bone metastases than visceral sites (27% versus 0%, P = 0.037).

Conclusions: These results indicate that CXCR4 can contribute to the homing of breast cancer cells to the bone. This finding might have important clinical implications since patients with metastatic bone disease may achieve the highest benefit from a CXCR4-targeted therapy.

Key words: bone metastases, CCR7, CXCR4, HER2-neu, metastatic breast cancer

{dagger} Present address: Haseki Research Hospital, Istanbul, Turkey.

Received for publication July 18, 2008. Revision received October 30, 2008. Accepted for publication November 6, 2008.


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