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Prolonged tamoxifen treatment increases relapse-free survival for patients with primary breast cancer expressing high levels of VEGF
Karolinska Institute.
Kalmar Hospital.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
Ctr Rene Huguenin, Lab Oncogenet, St Cloud, France.
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2010 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 46, no 9, 1580-1587 p.Article in journal (Refereed) Published
Abstract [en]

Previous retrospective studies have shown that high intratumoural levels of vascular endothelial growth factor (VEGF) correlate with an inferior outcome for patients treated with adjuvant tamoxifen. Our objectives were to validate the impact of VEGF on survival after adjuvant tamoxifen and to investigate the interaction between VEGF and treatment duration. For this purpose tumour homogenates from 402 patients with operable oestrogen receptor positive breast cancer (BC), treated with tamoxifen for 2 (n = 149) or 5 years (n = 253) as the only systemic adjuvant therapy were included. The median follow-up time for surviving patients was 9.8 years (range 0.5-14.8 years). Expression of VEGF was assessed by an enzyme-linked immunosorbent assay and investigated in relation to the standard BC parameters and survival. In the total population, higher VEGF was significantly correlated with shorter recurrence-free survival (RFS) (HR = 1.63, 95%CI = 1.11-2.39, p = 0.010), breast cancer corrected survival (BCCS) (HR = 1.82, 95%CI = 1.13-2.93, p = 0.014) and overall survival (OS) (HR = 1.51, 95%CI = 1.11-2.05, p = 0.009). High VEGF was significantly associated with reduced RFS (HR = 2.61, 95%CI = 1.45-4.70, p = 0.001) after two years of tamoxifen, whilst no difference was seen in patients treated for five years (HR = 1.09, 95%CI = 0.64-1.84, p = 0.760). A statistically significant interaction was observed between high VEGF expression and improved RFS after 5-year tamoxifen (p = 0.034). In concordance with previous studies, high VEGF was significantly correlated with shorter survival. We present data not reported previously revealing that patients expressing high levels of VEGF display a better outcome provided that tamoxifen is given for five years. Further studies on the impact of VEGF on a 5-year regimen are motivated.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 46, no 9, 1580-1587 p.
Keyword [en]
Endocrine resistance; VEGF; Tamoxifen; Endocrine therapy; Growth factor
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-58269DOI: 10.1016/j.ejca.2010.03.014ISI: 000279387700021OAI: diva2:337947
Available from: 2010-08-10 Created: 2010-08-09 Last updated: 2010-08-10

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Fohlin, HelenaNordenskjöld, BoStål, Olle
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Department of Clinical and Experimental MedicineFaculty of Health SciencesDepartment of Oncology UHLOncology
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