Vascular endothelial growth factor expression and T-regulatory cells in premenopausal breast cancer.

Estradiol (E2) plays a key role in human reproduc- tion through the induction of vascular endothelial growth factor (VEGF) and T-regulatory cells (T-Regs), which are also important in breast cancer (BC) growth. The primary endpoint of the present st udy was the investigation of whether E2 suppression, chemotherapy and radiation therapy decreased the levels of VEGF and T-Regs of premenopausal patients with high-risk early BC. The secondary endpoints were toxicity, progression-free survival (PFS) and overall sur vival (OS). Between Apr il 20 03 and July 20 08, 10 0 premenopausal women with early, high-risk BC were entered into the study. The characteristics of the patients were as follows: median age, 43 years (range, 26-45); median number of positive axillary nodes, 3.3; median Ki-67, 33%. Plasma E2, VEGF and T-Reg were measured at baseline and every year. Treatment comprised luteneizing hormone-releasing hormone (LH-RH) analogue, tailored chemotherapy, radiation therapy and hormonal therapy in oestrogen receptor-positive (ER+) tumours. At 4 years, a statistically significant decrease in E2, VEGF and T-Reg levels was observed; the PFS and OS rates were 94 and 98%, respectively. Hot flushes and G1 osteopenia occurred following LH-RH analogue administra- tion, while no unexpected toxicity was observed following chemotherapy. E2 deprivation with an LH-RH analogue, tailored chemotherapy, radiation therapy and hor monal therapy in ER+ tumours decreased plasma VEGF levels and T-Regs numbers in premenopausal high-risk ER+ and ER- BC patients. In addition, a favorable impact on PFS and OS was observed.