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
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)..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 29. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yadav, Kritika [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-820044/v1 |
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| PPN (Katalog-ID): |
XRA033557527 |
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| 245 | 1 | 0 | |a 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 |
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| 520 | |a 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). | ||
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