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Annals of Oncology Advance Access originally published online on June 23, 2009
Annals of Oncology 2009 20(10):1639-1646; doi:10.1093/annonc/mdp062
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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

Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer

B. K. Linderholm1,*, H. Hellborg2, U. Johansson2, G. Elmberger3, L. Skoog3, J. Lehtiö1 and R. Lewensohn1

1 Karolinska Biomic Centre
2 Regional Oncologic Centre
3 Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden

* Correspondence to: Dr B. K. Linderholm, Karolinska Biomic Centre, Karolinska University Hospital, SE-161 67 Stockholm, Sweden. Tel: +46-8-51777029; Fax: +46-8-5177100; E-mail: barbro.linderholm{at}ki.se

Background: Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC.

Patients and methods: VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients.

Results: Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/µg DNA compared with 2.7 pg/µg DNA in non-TNBC (P < 0.001). Patients with TNBC had statistically significant shorter recurrence-free survival [hazard ratio (HR) = 1.8; P = 0.0023], breast cancer-corrected survival (HR = 2.2; P = 0.004) and overall survival (HR = 1.8; P = 0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P = 0.087).

Conclusions: Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.

Key words: angiogenesis, survival, triple-negative breast cancer, VEGF

Received for publication November 25, 2008. Revision received February 2, 2009. Accepted for publication February 17, 2009.


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