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document
Anti-angiogenic effect of tamoxifen combined with epirubicin in breast cancer patients . Vascular endothelial growth factor A ( VEGF-A ) and vascular endothelial growth factor receptor 2 ( VEGFR2 ) are the key factors mediating neo-vascularization . They are often coexpressed in breast cancer . Sex steroids may stimulate angiogenesis via the estrogen receptor ( ER ) pathway . We investigated to compare the effects of the addition of tamoxifen to epirubicin versus epirubicin alone on VEGF and VEGFR2 expression in breast cancer patients . The expression of VEGF and VEGFR2 was assessed on tissue microarray by immunohistochemistry at baseline conditions and after treatments in the case of 191 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin plus tamoxifen as primary systemic treatment . Epirubicin alone failed to induce changes in VEGF expression ( P = 0.54 ) , while the addition of tamoxifen to epirubicin resulted in a significant reduction in VEGF expression ( P < 0.001 ) . As a consequence , baseline VEGF had a negative prognostic role in patients who received epirubicin alone but not in patients receiving epirubicin plus tamoxifen ( interaction test P < 0.05 ) . VEGFR2 expression increased at residual tumor histology in both treatment arms , with a lesser extent in patients receiving tamoxifen plus epirubicin . Decrease in VEGFR2 expression was significantly associated with response rate ( P = 0.02 ) . The addition of tamoxifen to epirubicin resulted in a suppression of a key angiogenic pathway . These data suggest a potential synergism of these two drugs .
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Intervention_Pharmacological
tamoxifen combined with epirubicin
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Intervention_Pharmacological
tamoxifen to epirubicin versus epirubicin alone
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Intervention_Pharmacological
tamoxifen to epirubicin
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Intervention_Pharmacological
epirubicin plus tamoxifen
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Intervention_Pharmacological
tamoxifen plus epirubicin
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Intervention_Pharmacological
addition of tamoxifen to epirubicin
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Outcome_Physical
VEGF and VEGFR2
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Outcome_Physical
changes in VEGF expression
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Outcome_Physical
VEGF expression
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Outcome_Physical
baseline VEGF
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Outcome_Physical
VEGFR2 expression
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Outcome_Physical
VEGFR2 expression
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Outcome_Physical
response rate
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Participant_Condition
breast cancer
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Participant_Sample-size
191
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Participant_Condition
T2-4 N0-1 breast cancer