Elevated Plasma Transforming Growth Factor-β1 Levels in Breast Cancer Patients Decrease After Surgical Removal of the Tumor

Abstract

The authors determined whether untreated breast cancer patients have elevated plasma levels of transforming growth factor-β1, (TGF-β1). Increased plasma TGF-β1 levels recently were found after chemotherapy in patients with advanced breast cancer. However, it currently is unknown whether this elevation in plasma TGF-β1 is caused by chemotherapy-induced normal tissue damage or whether it results from the presence of the tumor. An enzyme-linked immunosorbent assay was used to measure plasma TGF-β1 levels in 26 newly diagnosed breast cancer patients before and after definitive surgery. Patients were grouped by postoperative tumor status: 1) negative lymph nodes (group 1); 2) positive lymph nodes (group 2); and 3) overt residual disease (group 3). The site of TGF-β1 production in the tumors was localized by immunohistochemistry and in situ hybridization. Plasma TGF-β1 levels were elevated preoperatively in 81% of the patients; TGF-β2 and TGF-β3 were undetectable. The preoperative TGF-β1, levels in the three patient groups were similar; however, the postoperative plasma TGF-β1 levels differed by disease status. The mean plasma TGF-β1 level in group 1 (n = 12) normalized after surgery (19.3 ± 3.2 vs. 5.5 ± 1.0 ng/mL, p < 0.001). In contrast, the mean plasma TGF-β1 levels remained above normal in both group 2 (n = 9) and group 3 (n = 5) after surgery. Transforming growth factor-β1 expression was found to be preferentially increased in the tumor stroma. Breast tumors result in increased plasma TGF-β1 levels in 81% of patients. After surgical removal of the primary tumor, the plasma TGF-β1 level normalizes in the majority of patients; persistently elevated levels correlate with the presence of lymph node metastases or overt residual tumor.