Elevated plasma levels of TGF-beta1 in patients with locally advanced breast cancer related to other clinical stages

Background: The application of plasma tumor markers is mainly during the follow-up of cancer patients and especially in monitoring of advanced disease. These biomarkers do not require surgical intervention and provide relatively simple monitoring at any time during the disease course. TGF-beta1 is a pluripotent cytokine, with diverse effects in normal physiology and a role in both normal mammary gland development and progression of breast cancer. In early stages of breast carcinomas TGF-beta1 acts as tumor suppressor, while in later stages, when tumor cells become resistant to growth inhibition by TGF-beta1, it acts as tumor promoter. For that reason, the aim of this study was to assess the stage-related TGF-beta1 elevation in circulation of breast cancer patients, during disease progression. Methods: We analyzed 52 breast cancer patients of different stages (I/II, III, IV) and 36 healthy donors. TGF-beta1 levels were determined by enzyme-linked immunosorbent assay (ELISA, R&D). Results Although there was no increase in plasma TGF-beta1 in stage I/II patients (n =10, median value = 0.89 ng/ml), statistically significant elevation of plasma TGF-beta1 was found in locally advanced breast cancer (stage III, n = 9, median value = 2.30 ng/ml) and also in metastatic breast cancer (stage IV, n = 33, median value = 2.46 ng/ml) in relation to healthy donors and stage I/II. Conclusion: This elevation of plasma TGF-beta1 in locally advanced breast cancer is probably the result of increased tumor mass and tumor-stromal interactions in this stage, as well as a possible cause of greater metastatic potential of tumor cells which lead to metastatic breast cancer. Prognostic role of TGF-beta1 is not fully understood, but from these results we could say that it could be a marker for monitoring patients disease course, as well as for understating the biology of breast cancer.