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
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
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.
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
IdentifiersURN: urn:nbn:se:umu:diva-5966DOI: 10.1007/s10549-004-1655-7PubMedID: 15692755OAI: oai:DiVA.org:umu-5966DiVA: diva2:145634