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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.
Aula, H., Skyttä, T., Tuohinen, S., Luukkaala, T., Hämäläinen, M., Virtanen, V., … Kellokumpu-Lehtinen, P. L. (2019). Transforming growth factor beta 1 levels predict echocardiographic changes at three years after adjuvant radiotherapy for breast cancer. Radiation Oncology, 14(1). https://doi.org/10.1186/s13014-019-1366-1