Breast Cancer Treatment Decreases Serum Levels of TGF-ß1, VEGFR2, and TIMP-2 Compared to Healthy Volunteers: Significance for Therapeutic Outcomes?

Various complications from a breast cancer treatment, in the pathogenesis of which excessive tissue fibrosis plays a leading role, are a common pathology. In this study, the levels of TGF-ß1, VEGFR-2, and TIMP-2 were determined by the immuno-enzyme serum analysis for patients during the long-term period after breast cancer treatment as potential markers of fibrosis. The single-center study enrolled 92 participants, which were divided into two age-matched groups: (1) 67 patients following breast cancer treatment, and (2) 25 healthy female volunteers. The intergroup analysis demonstrated that the patients after breast cancer treatment showed a decrease in the serum levels of TGF-ß1 (U = 666, p < 0.001) and TIMP-2 (U = 637, p < 0.001) as compared to the group of healthy volunteers. The levels of VEGFR-2 in these groups were comparable (U = 1345, p = 0.082). It was also found that the type of treatment, the presence of lymphedema, shoulder joint contracture, and changes in lymphoscintigraphy did not affect the levels of TGF-ß1, VEGFR-2, and TIMP-2 within the group of patients after breast cancer treatment. These results may indicate that these biomarkers do not play a leading role in the maintenance and progression of fibrosis in the long-term period after breast cancer treatment. The reduced levels of TGF-ß1 and TIMP-2 may reflect endothelial dysfunction caused by the antitumor therapy.

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors.

Breast cancer (BC) is the most common tumor in women worldwide with high mortality rates. Surgical methods followed by radio-chemotherapy are used to treat these tumors. Such treatment can lead to various side effects, including neurological complications. The development of a reliable biomarker to predict the onset of CNS complications could improve clinical outcomes. In the current study, ICAM-1 and PECAM-1 serum levels were measured as potential biomarkers in 45 female patients in a long-term follow-up period after breast cancer treatment, and compared to 25 age-matched female healthy volunteers. Serum levels of both biomarkers, ICAM-1 and PECAM-1 were significantly higher in patients after breast cancer treatment and could be associated with cognitive dysfunction, depression, and vestibulocerebellar ataxia. In conclusion, our results provide a first hint that elevated serum levels of ICAM-1 and PECAM-1 could serve as early predictive biomarkers in breast cancer survivors that might help to improve the management of these patients.

Potential Molecular Biomarkers of Central Nervous System Damage in Breast Cancer Survivors.

Damage of the central nervous system (CNS), manifested by cognitive impairment, occurs in 80% of women with breast cancer (BC) as a complication of surgical treatment and radiochemotherapy. In this study, the levels of ICAM-1, PECAM-1, NSE, and anti-NR-2 antibodies which are associated with the damage of the CNS and the endothelium were measured in the blood by ELISA as potential biomarkers that might reflect pathogenetic mechanisms in these patients. A total of 102 patients enrolled in this single-center trial were divided into four groups: (1) 26 patients after breast cancer treatment, (2) 21 patients with chronic brain ischemia (CBI) and asymptomatic carotid stenosis (ICA stenosis) (CBI + ICA stenosis), (3) 35 patients with CBI but without asymptomatic carotid stenosis, and (4) 20 healthy female volunteers (control group). Intergroup analysis demonstrated that in the group of patients following BC treatment there was a significant increase of ICAM-1 (mean difference: −368.56, 95% CI −450.30 to −286.69, p < 0.001) and PECAM-1 (mean difference: −47.75, 95% CI −68.73 to −26.77, p < 0.001) molecules, as compared to the group of healthy volunteers. Additionally, a decrease of anti-NR-2 antibodies (mean difference: 0.89, 95% CI 0.41 to 1.48, p < 0.001) was detected. The intergroup comparison revealed comparable levels of ICAM-1 (mean difference: −33.58, 95% CI −58.10 to 125.26, p = 0.76), PECAM-1 (mean difference: −5.03, 95% CI −29.93 to 19.87, p = 0.95), as well as anti-NR-2 antibodies (mean difference: −0.05, 95% CI −0.26 to 0.16, p = 0.93) in patients after BC treatment and in patients with CBI + ICA stenosis. The NSE level in the group CBI + ICA stenosis was significantly higher than in women following BC treatment (mean difference: −43.64, 95% CI 3.31 to −83.99, p = 0.03). Comparable levels of ICAM-1 were also detected in patients after BC treatment and in the group of CBI (mean difference: −21.28, 95% CI −111.03 to 68.48, p = 0.92). The level of PECAM-1 molecules in patients after BC treatment was also comparable to group of CBI (mean difference: −13.68, 95% CI −35.51 to 8.15, p = 0.35). In conclusion, among other mechanisms, endothelial dysfunction might play a role in the damage of the CNS in breast cancer survivors.