Transforming growth factor-beta 1 (TGF-β1) has a dual role in cancer progression, with inhibitory functions in early tumor stages and tumor promotion in advanced stages. However, most prior studies have studied survival in either all tumor stages together or a subset of stages. Therefore, this study examined the effect of TGF-β1 before and after radiotherapy (RT) on progression-free survival (PFS) in a racially/ethnically diverse breast cancer patient population and stratified by cancer stage (n=488). Plasma samples were collected on the first (pre-RT) and last day of RT (post-RT), and patients were followed for up to 10 years through electronic medical records. TGF-β1 was assayed with the ELISA kit (R&D Systems, Inc, Minneapolis, MN). PFS was calculated as the time between the date of diagnosis to the first event (death, recurrence, or metastasis) or last follow-up if no event occurred. TGF-β1 was treated as a continuous variable (per 1,000 pg/mL increase). Univariable and multivariable Cox proportional hazards regression models were used to evaluate the association between TGF-β1 and PFS, adjusted for age at diagnosis, clinical tumor stage, and triple-negative breast cancer status in total, stage 0-II, or stage III-IV patients. The study population was comprised of 306 Hispanic white (63%), 102 Black/African American (21%), 64 non-Hispanic white (13%), and 16 other patients (3%). In univariable analyses, stage 0-II patients had 12% and 11% higher risk for event for every 1,000 pg/mL increase in pre-RT (HR=1.12, 95%CI=1.05-1.19, p<0.001) and post-RT (HR=1.11, 95%CI=1.01-1.23, p=0.034) TGF-β1, respectively. In multivariable models, increases in pre-RT (HR=1.11, 95%CI=1.04-1.19, p<0.001) and post-RT TGF-β1 (HR=1.12, 95%CI=1.01-1.24, p=0.031) remained significantly associated with worse PFS in stage 0-II patients, and post-RT TGF-β1 became significantly associated with worse PFS in all patients (HR=1.10, 95%CI=1.00-1.20, p=0.048). In a subset of 107 patients, there was a significant drop of TGF-β1 levels from baseline before any treatment to pre-RT (mean±SD: 6269±3296 to 3787±2810, p<0.001). The implication is that other treatment(s) before RT reduced the tumor burden that may contribute to decreasing circulating TGF-β1 levels. However, TGF-β1 levels were not different between pre- and post-RT. In summary, our current data suggest that higher pre- and post-RT TGF-β1 levels were associated with worse PFS in early-stage patients. Although plasma TGF-β1 levels may not represent the amount of TGF-β1 in tumor, it may still serve as a surrogate prognostic marker and a potential target in cancer therapy. Future larger studies are warranted to validate our findings that circulating TGF-β1 may predict progression-free survival of breast cancer, especially in patients with early stage tumors.

Citation Format: George Ruochen Yang, Cristiane Takita, Jean L. Wright, Isildinha M. Reis, Eunkyung Lee, Jennifer J. Hu. Association between transforming growth factor beta 1 and progression-free survival in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 897.