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Annals of Oncology Advance Access originally published online on March 9, 2007
Annals of Oncology 2007 18(6):1021-1029; doi:10.1093/annonc/mdm060
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© 2007 European Society for Medical Oncology

breast cancer

Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer

N Cabioglu1,{dagger},{ddagger}, Y Gong1,{dagger}, R Islam2, KR Broglio3, N Sneige1, A Sahin1, AM Gonzalez-Angulo2, P Morandi4, C Bucana5, GN Hortobagyi2 and M Cristofanilli2,*

1 Department of Pathology
2 Department of Breast Medical Oncology
3 Department of Biostatistics and Applied Mathematics
5 Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
4 St Bartolo Hospital, Vicenza, Italy

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

Purpose: Recent studies have indicated that expression of chemokine receptors CXCR4 and CCR7 could be an indicator of the metastatic potential of breast cancer. Expression of CXCR4 and CCR7 along with the biomarkers HER2-neu and epidermal growth factor receptor (EGFR) was investigated in inflammatory breast cancer (IBC) to evaluate their prognostic implications.

Experimental design: CXCR4, CCR7, and EGFR were evaluated by immunohistochemical staining (IHC) of paraffin-embedded tissue sections. HER2-neu amplification was assessed by FISH and/or IHC. All patients received chemotherapy, surgery, and radiation.

Results: Forty-four cases diagnosed with IBC from 1994 to 2002 were included in the study. In all, 18 (40.9%) patients had positive CXCR4, 10 (22.7%) had positive CCR7, 21 (47.7%) had positive HER2-neu, and EGFR was positive in 12 of 40 patients (30%). The 5-year overall survival (OS) was 24.8% for CXCR4-positive disease versus 42.3% for CXCR4-negative patients (P = 0.53) and 20.0% for CCR7-positive disease versus 41.9% for CCR7-negative patients (P = 0.24). EGFR-positive disease had significantly worse OS compared with EGFR-negative disease (P = 0.01).

Conclusions: These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.

Key words: CCR7, CXCR4, EGFR, HER2-neu, inflammatory breast cancer

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Department of Surgery, Haseki Research Hospital, Istanbul, Turkey.

Received for publication October 14, 2006. Revision received January 15, 2007. Accepted for publication January 22, 2007.


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