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Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort

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Title: Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort
Authors: Drake, Rebecca J.G., Landén, Amalia H., Holmberg, Erik, Tullberg, Axel Stenmark, Killander, Fredrika, Niméus, Emma, Jordan, Alexander, McGuinness, Jennifer, Karlsson, Per, Hodivala-Dilke, Kairbaan
Contributors: Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast cancer treatment, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancerbehandling, Originator, Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Biomarkers and epidemiology, Breast cancer Proteogenomics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Biomarkörer och Epi, Bröstcancer Proteogenomik, Originator
Source: Clinical Cancer Research. 31(7):1323-1332
Subject Terms: Medical and Health Sciences, Clinical Medicine, Cancer and Oncology, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Basic Medicine, Medical Genetics and Genomics (including Gene Therapy), Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik och genomik (Här ingår: Genterapi)
Description: Purpose: Identifying biomarkers of radiotherapy (RT) response is important for optimizing the treatment of early breast cancer. In this study, we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomized study. Preclinical data suggest an enhanced effect of RT on low EC_pY397-FAK expression. Experimental Design: We analyzed tissue microarrays from the Swedish Breast Cancer Group 91 Radiotherapy (stage I–II, lymph node–negative) breast cancer cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT. Tissue microarray sections were immunostained for pY397-FAK, CD31, α-smooth muscle actin, and pan-cytokeratin. HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, pan-cytokeratin–positive tumor epithelial cells, and α-smooth muscle actin + mural/stromal cells per core. For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence and all recurrence, respectively, as dependent variables and RT and EC_pY397-FAK as independent variables. Results: EC_pY397-FAK expression was not predictive for the primary endpoint locoregional recurrence (P ¼ 0.098), but the direction of the RT effect was in line with preclinical findings. For the secondary endpoint all recurrence, there was a significant interaction (P ¼ 0.026) between EC_pY397-FAK and RT. Without RT, higher EC_pY397-FAK expression resulted in a lower risk for all recurrence (HR ¼ 0.74 per SD; 95% confidence interval ¼ 0.57–0.96; P ¼ 0.026). Conclusions: Within the first 5 years following BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression. However, without RT, low EC_pY397-FAK expression is associated with a higher risk of recurrence.
Access URL: https://doi.org/10.1158/1078-0432.CCR-24-2939
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  Data: Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort
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  Data: <searchLink fieldCode="AR" term="%22Drake%2C+Rebecca+J%2EG%2E%22">Drake, Rebecca J.G.</searchLink><br /><searchLink fieldCode="AR" term="%22Landén%2C+Amalia+H%2E%22">Landén, Amalia H.</searchLink><br /><searchLink fieldCode="AR" term="%22Holmberg%2C+Erik%22">Holmberg, Erik</searchLink><br /><searchLink fieldCode="AR" term="%22Tullberg%2C+Axel+Stenmark%22">Tullberg, Axel Stenmark</searchLink><br /><searchLink fieldCode="AR" term="%22Killander%2C+Fredrika%22">Killander, Fredrika</searchLink><br /><searchLink fieldCode="AR" term="%22Niméus%2C+Emma%22">Niméus, Emma</searchLink><br /><searchLink fieldCode="AR" term="%22Jordan%2C+Alexander%22">Jordan, Alexander</searchLink><br /><searchLink fieldCode="AR" term="%22McGuinness%2C+Jennifer%22">McGuinness, Jennifer</searchLink><br /><searchLink fieldCode="AR" term="%22Karlsson%2C+Per%22">Karlsson, Per</searchLink><br /><searchLink fieldCode="AR" term="%22Hodivala-Dilke%2C+Kairbaan%22">Hodivala-Dilke, Kairbaan</searchLink>
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  Data: Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast cancer treatment, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancerbehandling, Originator<br />Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator<br />Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Biomarkers and epidemiology, Breast cancer Proteogenomics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Biomarkörer och Epi, Bröstcancer Proteogenomik, Originator
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  Data: <i>Clinical Cancer Research</i>. 31(7):1323-1332
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– Name: Abstract
  Label: Description
  Group: Ab
  Data: Purpose: Identifying biomarkers of radiotherapy (RT) response is important for optimizing the treatment of early breast cancer. In this study, we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomized study. Preclinical data suggest an enhanced effect of RT on low EC_pY397-FAK expression. Experimental Design: We analyzed tissue microarrays from the Swedish Breast Cancer Group 91 Radiotherapy (stage I–II, lymph node–negative) breast cancer cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT. Tissue microarray sections were immunostained for pY397-FAK, CD31, α-smooth muscle actin, and pan-cytokeratin. HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, pan-cytokeratin–positive tumor epithelial cells, and α-smooth muscle actin + mural/stromal cells per core. For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence and all recurrence, respectively, as dependent variables and RT and EC_pY397-FAK as independent variables. Results: EC_pY397-FAK expression was not predictive for the primary endpoint locoregional recurrence (P ¼ 0.098), but the direction of the RT effect was in line with preclinical findings. For the secondary endpoint all recurrence, there was a significant interaction (P ¼ 0.026) between EC_pY397-FAK and RT. Without RT, higher EC_pY397-FAK expression resulted in a lower risk for all recurrence (HR ¼ 0.74 per SD; 95% confidence interval ¼ 0.57–0.96; P ¼ 0.026). Conclusions: Within the first 5 years following BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression. However, without RT, low EC_pY397-FAK expression is associated with a higher risk of recurrence.
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      – TitleFull: Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort
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