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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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- Rydén, Lisa (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund
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- Stendahl, Maria (author)
- Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
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- Jonsson, Håkan (author)
- Umeå universitet,Kirurgi,Onkologi
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- The Hague : Nijhoff, 2005
- 2005
- English.
- In: Breast Cancer Research and Treatment. - The Hague : Nijhoff. - 0167-6806 .- 1573-7217. ; 89:2, s. 135-143
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Aged
- Antineoplastic Agents; Hormonal/*pharmacology/*therapeutic use
- Breast Neoplasms/*drug therapy/*pathology
- Chemotherapy; Adjuvant
- Female
- Follow-Up Studies
- Humans
- Immunohistochemistry
- Middle Aged
- Postmenopause
- Prognosis
- Tamoxifen/*pharmacology/*therapeutic use
- Treatment Outcome
- Tumor Markers; Biological/*analysis
- Vascular Endothelial Growth Factor A/*blood
- Vascular Endothelial Growth Factor Receptor-2/*blood
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Jonsson, Håkan
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