Transforming growth factor beta 1 levels predict echocardiographic changes at three years after adjuvant radiotherapy fo
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RESEARCH
Open Access
Transforming growth factor beta 1 levels predict echocardiographic changes at three years after adjuvant radiotherapy for breast cancer Hanna Aula1,2* , Tanja Skyttä1,2, Suvi Tuohinen3,4, Tiina Luukkaala5,6, Mari Hämäläinen7, Vesa Virtanen3, Pekka Raatikainen4, Eeva Moilanen7 and Pirkko-Liisa Kellokumpu-Lehtinen1,2
Abstract Background: Transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are cytokines involved in fibrotic processes causing radiotherapy (RT)-induced cardiovascular changes. We aimed to investigate the associations between TGF-β1 and PDGF and the echocardiographic changes that occur during RT and during three-year follow-up. Methods: The study included 63 women receiving adjuvant RT for early-stage breast cancer or ductal carcinoma in situ. Serum TGF-β1 (ng/ml) and PDGF (ng/ml) levels were measured by enzyme-linked immunoassay and echocardiographic examination was performed before RT, after RT and at 3 years. Patients were grouped by biomarker behavior by a trajectory analysis. Results: TGF-β1 decreased from 19.2 (IQR 17.1–22.3) before RT to 18.8 (14.5–22.0) after RT (p = 0.003) and the decrease persisted at 17.2 (13.7–21.2) 3 years after RT (p = 0.101). PDGF decreased from 15.4 (12.6–19.1) before RT to 13.8 (11.7–16.2) after RT, p = 0.001, and persisted at 15.6 (10.4–18.4) at 3 years, p = 0.661. The TGF-β1 level before RT (Spearman’s rho 0.441, p < 0.001) and the three-year change in TGF-β1 (rho = − 0.302, p = 0.018) correlated with global longitudinal strain (GLS) in echocardiography at 3 years. In trajectory analysis, two TGF-β1 behavior groups were found. Group 1 had significantly higher TGF-β1 levels before RT, 25.6 (22.3–28.6), than group 2, 17.8 (15.9–19.9), p < 0.001. In multivariable analysis, TGF-β1 trajectory group 1 (β = 0.27, p = 0.013), left-sided breast cancer (β = 0.39, p = 0.001) and the use of aromatase inhibitors (β = 0.29, p = 0.011) were significantly associated with a worsening in GLS from before RT to 3 years. Conclusion: An elevated pretreatment TGF-β1 may predict RT-associated changes in echocardiography. Keywords: Transforming growth factor beta 1, Platelet-derived growth factor, Cardiotoxicity, Breast cancer, Radiotherapy, Echocardiography
* Correspondence: [email protected] 1 Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland 2 Department of Oncology, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org
