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Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up. Implication of a link between VEGF pathway and tamoxifen response

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Abstract

Vascular endothelial growth factor (VEGF-A) is considered a prognostic indicator for clinical outcome in breast cancer. Conflicting results nevertheless exist and there is a need for larger studies including untreated patients in order to clarify the importance of tumor-specific VEGF-A regarding prognosis as well as potential links to predictive treatment information. VEGF-A and its receptor, vascular endothelial growth receptor 2 (VEGFR2), were therefore analyzed by immunohistochemistry in postmenopausal breast cancers enrolled in a clinical trial where patients were randomized to adjuvant tamoxifen treatment (n=124) for 2 years or no treatment (n=127) with a median follow-up of 18 years. The tumors were arranged in a tumor tissue microarray system enabling parallell analysis of the angiogenic factors and hormone receptor status. Tumor-specific expression of VEGFR2 correlated strongly with expression of VEGF-A and progesterone receptor (PR) negativity, whereas VEGF-A was not associated with hormone receptor status. Among patients with estrogen receptor (ER) positive (fraction > 10%) tumors, there was a statistically significant tamoxifen response in VEGF-A negative tumors at both 10-year and 18-year disease-free survival (DFS), contrasting to VEGF-A positive tumors who had no beneficial effect of tamoxifen. A treatment-interaction variable indicated a marked difference in tamoxifen response depending on VEGFA-status in terms of DFS at 10 and 18 years of follow-up, p=0.046 and p=0.039, respectively. VEGFR2 status did not yield significant predicitve information for tamoxifen response in patients with ER fraction > 10%, whereas in patients with ER fraction > 90% both VEGF-A and VEGFR2 status were associated with tamoxifen treatment effect.

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Authors and Affiliations

  1. Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö, University Hospital, SE – 205 02, Malmö, Sweden

    Lisa Rydén, Maria Stendahl & Göran Landberg

  2. Departments of Oncology and Surgery, Umeå University, Umeå, Sweden

    Håkan Jonsson, Stefan Emdin & Nils O Bengtsson

Authors
  1. Lisa Rydén
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  2. Maria Stendahl
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  3. Håkan Jonsson
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  4. Stefan Emdin
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  5. Nils O Bengtsson
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  6. Göran Landberg
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Correspondence to Lisa Rydén.

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Rydén, L., Stendahl, M., Jonsson, H. et al. Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up. Implication of a link between VEGF pathway and tamoxifen response. Breast Cancer Res Treat 89, 135–143 (2005). https://doi.org/10.1007/s10549-004-1655-7

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  • DOI: https://doi.org/10.1007/s10549-004-1655-7

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