Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer

Abstract Background Radiation-induced heart disease is mainly caused by activation of the fibrotic process. Transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are pro-fibrotic mediators. The aim of our study was to evaluate the behavior of TGF-β1 and PDGF during adj...

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Main Authors: Hanna Aula, Tanja Skyttä, Suvi Tuohinen, Tiina Luukkaala, Mari Hämäläinen, Vesa Virtanen, Pekka Raatikainen, Eeva Moilanen, Pirkko-Liisa Kellokumpu-Lehtinen
Format: Article
Language:English
Published: BMC 2018-10-01
Series:Radiation Oncology
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Online Access:http://link.springer.com/article/10.1186/s13014-018-1150-7
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author Hanna Aula
Tanja Skyttä
Suvi Tuohinen
Tiina Luukkaala
Mari Hämäläinen
Vesa Virtanen
Pekka Raatikainen
Eeva Moilanen
Pirkko-Liisa Kellokumpu-Lehtinen
author_facet Hanna Aula
Tanja Skyttä
Suvi Tuohinen
Tiina Luukkaala
Mari Hämäläinen
Vesa Virtanen
Pekka Raatikainen
Eeva Moilanen
Pirkko-Liisa Kellokumpu-Lehtinen
author_sort Hanna Aula
collection DOAJ
description Abstract Background Radiation-induced heart disease is mainly caused by activation of the fibrotic process. Transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are pro-fibrotic mediators. The aim of our study was to evaluate the behavior of TGF-β1 and PDGF during adjuvant radiotherapy (RT) for breast cancer and the association of these cytokines with echocardiographic changes. Methods Our study included 73 women with early-stage breast cancer or ductal carcinoma in situ (DCIS) receiving post-operative RT but not chemotherapy. TGF-β1 and PDGF levels in serum samples taken before and on the last day of RT were measured by an enzyme-linked immunosorbent assay. Echocardiography was also performed at same time points. Patients were grouped according to a ≥ 15% worsening in tricuspid annular plane systolic excursion (TAPSE) and pericardium calibrated integrated backscatter (cIBS). Results In all patients, the median TGF-β1 decreased from 25.0 (IQR 21.1–30.3) ng/ml to 23.6 (IQR 19.6–26.8) ng/ml (p = 0.003), and the median PDGF decreased from 18.0 (IQR 13.7–22.7) ng/ml to 15.6 (IQR 12.7–19.5) ng/ml (p < 0.001). The baseline TGF-β1, 30.7 (IQR 26.0–35.9) ng/l vs. 23.4 (IQR 20.1–27.3) ng/l (p < 0.001), and PDGF, 21.5. (IQR 15.7–31.2) ng/l vs. 16.9. (IQR 13.0–21.2) ng/ml, were higher in patients with a ≥ 15% decrease in TAPSE than in patients with a < 15% decrease. In patients with a ≥ 15% decrease in TAPSE, the median TGF-β1 decreased to 24.7 (IQR 20.0–29.8) ng/ml (p < 0.001), and the median PDGF decreased to 16.7 (IQR 12.9–20.9) ng/ml (p < 0.001). The patients with a < 15% decrease had stable TGF-β1 (p = 0.104), but PDGF decreased to 15.1 (IQR 12.5–18.6), p = 0.005. The patients with a ≥ 15% increase in cIBS exhibited a decrease in TGF-β1 from 26.0 (IQR 21.7–29.7) to 22.5 (IQR 16.6.-26.7) ng/ml, p < 0.001, and a decrease in PDGF from 19.8 (IQR 14.6–25.9) to 15.7 (IQR 12.8–20.2) ng/ml, p < 0.001. In patients with a < 15% increase, TGF-β1 and PDGF did not change significantly, p = 0.149 and p = 0.053, respectively. Conclusion We observed a decrease in TGF-β1 and PDGF levels during adjuvant RT for breast cancer. Echocardiographic changes, namely, in TAPSE and cIBS, were associated with a greater decrease in TGF-β1 and PDGF levels. Longer follow-up times will show whether these changes observed during RT translate into increased cardiovascular morbidity.
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spelling doaj.art-1a05fa01b77b42a2934beacb20ae4e4d2022-12-22T03:30:17ZengBMCRadiation Oncology1748-717X2018-10-0113111010.1186/s13014-018-1150-7Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancerHanna Aula0Tanja Skyttä1Suvi Tuohinen2Tiina Luukkaala3Mari Hämäläinen4Vesa Virtanen5Pekka Raatikainen6Eeva Moilanen7Pirkko-Liisa Kellokumpu-Lehtinen8Faculty of Medicine and Life Sciences, University of TampereFaculty of Medicine and Life Sciences, University of TampereFaculty of Medicine and Life Sciences, University of TampereResearch, Development and Innovation Center, Pirkanmaa Hospital DistrictThe Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University HospitalFaculty of Medicine and Life Sciences, University of TampereDepartment of Cardiology, Heart and Lung Center, Helsinki University HospitalThe Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University HospitalFaculty of Medicine and Life Sciences, University of TampereAbstract Background Radiation-induced heart disease is mainly caused by activation of the fibrotic process. Transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are pro-fibrotic mediators. The aim of our study was to evaluate the behavior of TGF-β1 and PDGF during adjuvant radiotherapy (RT) for breast cancer and the association of these cytokines with echocardiographic changes. Methods Our study included 73 women with early-stage breast cancer or ductal carcinoma in situ (DCIS) receiving post-operative RT but not chemotherapy. TGF-β1 and PDGF levels in serum samples taken before and on the last day of RT were measured by an enzyme-linked immunosorbent assay. Echocardiography was also performed at same time points. Patients were grouped according to a ≥ 15% worsening in tricuspid annular plane systolic excursion (TAPSE) and pericardium calibrated integrated backscatter (cIBS). Results In all patients, the median TGF-β1 decreased from 25.0 (IQR 21.1–30.3) ng/ml to 23.6 (IQR 19.6–26.8) ng/ml (p = 0.003), and the median PDGF decreased from 18.0 (IQR 13.7–22.7) ng/ml to 15.6 (IQR 12.7–19.5) ng/ml (p < 0.001). The baseline TGF-β1, 30.7 (IQR 26.0–35.9) ng/l vs. 23.4 (IQR 20.1–27.3) ng/l (p < 0.001), and PDGF, 21.5. (IQR 15.7–31.2) ng/l vs. 16.9. (IQR 13.0–21.2) ng/ml, were higher in patients with a ≥ 15% decrease in TAPSE than in patients with a < 15% decrease. In patients with a ≥ 15% decrease in TAPSE, the median TGF-β1 decreased to 24.7 (IQR 20.0–29.8) ng/ml (p < 0.001), and the median PDGF decreased to 16.7 (IQR 12.9–20.9) ng/ml (p < 0.001). The patients with a < 15% decrease had stable TGF-β1 (p = 0.104), but PDGF decreased to 15.1 (IQR 12.5–18.6), p = 0.005. The patients with a ≥ 15% increase in cIBS exhibited a decrease in TGF-β1 from 26.0 (IQR 21.7–29.7) to 22.5 (IQR 16.6.-26.7) ng/ml, p < 0.001, and a decrease in PDGF from 19.8 (IQR 14.6–25.9) to 15.7 (IQR 12.8–20.2) ng/ml, p < 0.001. In patients with a < 15% increase, TGF-β1 and PDGF did not change significantly, p = 0.149 and p = 0.053, respectively. Conclusion We observed a decrease in TGF-β1 and PDGF levels during adjuvant RT for breast cancer. Echocardiographic changes, namely, in TAPSE and cIBS, were associated with a greater decrease in TGF-β1 and PDGF levels. Longer follow-up times will show whether these changes observed during RT translate into increased cardiovascular morbidity.http://link.springer.com/article/10.1186/s13014-018-1150-7CardiotoxicityBreast cancerRadiotherapyTransforming growth factor beta-1Platelet-derived growth factorEchocardiography
spellingShingle Hanna Aula
Tanja Skyttä
Suvi Tuohinen
Tiina Luukkaala
Mari Hämäläinen
Vesa Virtanen
Pekka Raatikainen
Eeva Moilanen
Pirkko-Liisa Kellokumpu-Lehtinen
Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
Radiation Oncology
Cardiotoxicity
Breast cancer
Radiotherapy
Transforming growth factor beta-1
Platelet-derived growth factor
Echocardiography
title Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
title_full Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
title_fullStr Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
title_full_unstemmed Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
title_short Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
title_sort decreases in tgf β1 and pdgf levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer
topic Cardiotoxicity
Breast cancer
Radiotherapy
Transforming growth factor beta-1
Platelet-derived growth factor
Echocardiography
url http://link.springer.com/article/10.1186/s13014-018-1150-7
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