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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
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2005 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 89, no 2, 135-143 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
The Hague: Nijhoff , 2005. Vol. 89, no 2, 135-143 p.
Keyword [en]
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
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URN: urn:nbn:se:umu:diva-5966DOI: 10.1007/s10549-004-1655-7PubMedID: 15692755OAI: oai:DiVA.org:umu-5966DiVA: diva2:145634
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2017-12-14Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15692755&dopt=Citation

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