Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor.
OBJECTIVE
The authors determined whether untreated breast cancer patients have elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1).


BACKGROUND
Increased plasma TGF-beta 1 levels 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-beta 1 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-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 were undetectable. The preoperative TGF-beta 1 levels in the three patient 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 levels remained above normal in both group 2 (n = 9) and group 3 (n = 5) after surgery. Transforming growth factor-beta 1 expression was found to be preferentially increased in the tumor stroma.


CONCLUSIONS
Breast tumors result in increased plasma TGF-beta 1 levels in 81% of patients. After surgical removal of the primary tumor, the plasma TGF-beta 1 level normalizes in the majority of patients; persistently elevated levels correlate with the presence of lymph node metastases or overt residual tumor. These findings suggest that the usefulness of TGF-beta 1 as a potential plasma marker for breast tumors deserves further study.
Kong
F M
FM
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
Anscher
M S
MS
Murase
T
T
Abbott
B D
BD
Iglehart
J D
JD
Jirtle
R L
RL
D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D018567:Breast Neoplasms, Male / Q000097:blood / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000473:pathology / Q000556:secondary / Q000601:surgery; D018275:Carcinoma, Lobular / Q000097:blood / Q000473:pathology / Q000556:secondary / Q000601:surgery; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D015203:Reproducibility of Results; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000097:blood*
D014408:Biomarkers, Tumor; D016212:Transforming Growth Factor beta