ELEVATED PLASMA TRANSFORMING GROWTH FACTOR-BETA(1) LEVELS IN BREAST-CANCER PATIENTS DECREASE AFTER SURGICAL REMOVAL OF THE TWMOR

Objective The authors determined whether untreated breast cancer patie nts have elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)). Summary Background Data Increased plasma TGF-beta(1) le vels recently were found after chemotherapy in patients with advanced breast cancer. However, it currently is unknown whether this elevation in plasma TGF-beta(1) is caused by chemotherapy-induced normal tissue damage or whether it results from the presence of the tumor. Methods An enzyme-linked immunosorbent assay was used to measure plasma TGF-be ta(1) levels in 26 newly diagnosed breast cancer patients before and a fter definitive surgery. Patients were grouped by postoperative tumor status: 1) negative lymph nodes (group 1); 2) positive lymph nodes (gr oup 2); and 3) overt residual disease (group 3). The site of TGF-beta( 1) production in the tumors was localized by immunohistochemistry and in situ hybridization. Results Plasma TGF-beta(1) levels were elevated preoperatively in 81% of the patients; TGF-beta(2) and TGF-beta(3) we re undetectable. The preoperative TGF-beta(1) levels in the three pati ent groups were similar; however, the postoperative plasma TGF-beta(1) levels differed by disease status. The mean plasma TGF-beta(1) 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-beta(1) level s remained above normal in both group 2 (n = 9) and group 3 (n = 5) af ter surgery. Transforming growth factor-beta(1) expression was found t o be preferentially increased in the tumor stroma. Conclusions Breast tumors result in increased plasma TGF-beta(1) levels in 81% of patient s. After surgical removal of the primary tumor, the plasma TGF-beta(1) level normalizes in the majority of patients; persistently elevated l evels correlate with the presence of lymph node metastases or overt re sidual tumor. These findings suggest that the usefulness of TGF-beta(1 ) as a potential plasma marker for breast tumors deserves further stud y.