scholarly journals Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer

2021 ◽  
Author(s):  
Kritika Yadav ◽  
Joline Lim ◽  
Joan Choo ◽  
Samuel Guan Wei Ow ◽  
Andrea Wong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferation Index ◽  
Vascular Endothelial ◽  
Breast Cancer Patients ◽  
Tumor Vessel ◽  
Vascular Normalization ◽  
Pre Treatment ◽  
Dose Dense ◽  
Tumor Biopsies ◽  
Endothelial Growth Factor

Abstract Purpose Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky. Pre-treatment with anti-angiogenic agents can “normalize” the tumor vasculature allowing effective intra-tumoral delivery of standard chemotherapy. Immunohistochemistry (IHC) analysis was applied to investigate and compare the vascular normalization and anti-angiogenic effects of two commonly used anti-angiogenic agents, Sunitinib and Bevacizumab, administered prior to chemotherapy in HER2-negative breast cancer patients. Methods This prospective clinical trial enrolled 38 patients into a sunitinib cohort and 24 into a bevacizumab cohort. All received 4 cycles of doxorubicin/cyclophosphamide chemotherapy and pre-treatment with either sunitinib or bevacizumab. Tumor biopsies were obtained at baseline, after cycle 1 (C1) and cycle 4 (C4) of chemotherapy. IHC was performed to assess the tumor vascular normalization index (VNI), lymphatic vessel density (LVD), Ki67 proliferation index and expression of tumor VEGFR2. Results In comparison to Bevacizumab, Sunitinib led to a significant increase in VNI post-C1 and C4 (p < 0.001 and 0.001) along with decrease in LVD post-C1 (p = 0.017). Both drugs when combined with chemotherapy resulted in significant decline in tumor proliferation after C1 and C4 (baseline vs post-C4 Ki67 index p = 0.006 for Sunitinib vs p = 0.021 for Bevacizumab). Bevacizumab resulted in a significant decrease in VEGFR2 expression post-C1 (p = 0.004). Conclusion Sunitinib, in comparison to Bevacizumab showed a greater effect on tumor vessel modulation and lymphangiogenesis suggesting that its administration prior to chemotherapy might result in improved drug delivery. Trial registry ClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

scholarly journals Immunohistochemistry Study of Tumor Vascular Normalization and Anti-angiogenic Effects of Sunitinib Versus Bevacizumab Prior to Dose Dense Doxorubicin/cyclophosphamide Chemotherapy in HER2 Negative Breast Cancer

2021 ◽  
Author(s):  
Kritika Yadav ◽  
Joline Lim ◽  
Joan Choo ◽  
Samuel Guan Wei Ow ◽  
Andrea Wong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Vasculature ◽  
Proliferation Index ◽  
Vascular Endothelial ◽  
Tumor Vessel ◽  
Vascular Normalization ◽  
Pre Treatment ◽  
Dose Dense ◽  
Tumor Biopsies ◽  
Endothelial Growth Factor

Abstract PurposeTumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky. Pre-treatment with anti-angiogenic agents can “normalize” the tumor vasculature allowing effective intra-tumoral delivery of standard chemotherapy.Immunohistochemistry (IHC) analysis was applied to investigate and compare the vascular normalization and anti-angiogenic effects of two commonly used anti-angiogenic agents, Sunitinib and Bevacizumab, administered prior to chemotherapy in HER2 negative breast cancer patients.MethodsThis prospective clinical trial enrolled 38 patients into a sunitinib cohort and 24 into a bevacizumab cohort. All received 4 cycles of doxorubicin/cyclophosphamide chemotherapy and pre-treatment with either sunitinib or bevacizumab. Tumor biopsies were obtained at baseline, after cycle 1 (C1) and cycle 4 (C4) of chemotherapy. IHC was performed to assess the tumor vascular normalization index (VNI), lymphatic vessel density (LVD), Ki67 proliferation index and expression of tumor VEGFR2. ResultsIn comparison to Bevacizumab, Sunitinib led to a significant increase in VNI post C1 and C4 (p <0.001 and 0.001) along with decrease in LVD post C1 (p= 0.017). Both drugs when combined with chemotherapy resulted in significant decline in tumor proliferation after C1 and C4 (baseline vs post C4 Ki67 index p=0.006 for Sunitinib vs p=0.021 for Bevacizumab). Bevacizumab resulted in a significant decrease in VEGFR2 expression post C1 (p=0.004). ConclusionSunitinib, in comparison to Bevacizumab showed a greater effect on tumor vessel modulation and lymphangiogenesis suggesting that its administration prior to chemotherapy might result in improved drug delivery.Clinical trial registrationClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

Plasma vascular endothelial growth factor level and cognitive changes in breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20566-e20566
Author(s):  
Terence Ng ◽  
Yin Ting Cheung ◽  
Maung Shwe Ham Guo ◽  
Yuan Chuan Kee ◽  
Han Kiat Ho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cognitive Functioning ◽  
Cancer Patients ◽  
Response Speed ◽  
Vascular Endothelial ◽  
Breast Cancer Patients ◽  
Endothelial Growth Factor ◽  
Vegf Level

e20566 Background: It is suggested that vascular endothelial growth factor (VEGF) induces neurogenesis in the brain and provides neuroprotectiveeffects. This study was designed to examine the relation between plasma VEGF level and cognitive functioning in breast cancer patients who have received chemotherapy. Methods: Early-stage breast cancer patients (stage I to III) who received anthracycline- and/or taxane-based chemotherapy were prospectively recruited at a single center. Perceived cognitive functioning (FACT-Cog) and computerized neuropsychological assessment (Headminder) were used to evaluate patients’ cognitive function at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Headminder evaluated four cognitive domains: Attention, Memory, Processing, and Response speed. Impairment in each domain were defined as a >2.5 reduction of the Z score from baseline, as calculated by the reliable change index for repeated cognitive measurements. Plasma VEGF levels were analyzed at each time point using the multiplex immunoassay. Spearman Correlation (rs) was utilized to correlate the change in plasma VEGF and neurocognitive functioning. Results: Thirty-six patients were recruited (median age: 51.5; Chinese: 80.6%; post-menopausal: 58.3%). Median plasma VEGF levels were T1: 19.2 pg/ml; T2: 26.5 pg/ml; T3: 21.9 pg/ml. Weak correlations were observed between the change in VEGF level and the change in FACT-Cog and Headminder scores for individual cognitive domain (Table). Conclusions: Results suggest a weak correlation between plasma VEGF level and cognitive functioning in the domains of attention, concentration, functional interferences, mental acuity and response speed. Larger sample size and longer follow up are required to further explore the findings. [Table: see text]

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