The effect of menopause and hysterectomy on systemic vascular endothelial growth factor in women undergoing surgery for breast cancer

The aims of this study were to investigate circulating VEGF levels in breast cancer patients and assess the effect of menopause or hysterectomy on systemic VEGF.Patients undergoing primary surgery for breast cancer and controls matched for age, menopausal and hysterectomy status were prospectively recruited. Serum VEGF, FSH, LH, estrogen, progesterone and platelet levels were measured. Serum VEGF was corrected for platelet load (sVEGFp) to provide a biologically relevant measurement of circulating VEGF. SVEGFp levels were analyzed with respect to tumor characteristics, menopausal status and hysterectomy status.Two hundred women were included in the study; 89 breast cancer patients and 111 controls. SVEGFp levels were significantly higher in breast cancer patients compared to controls (p = 0.0001), but were not associated with clinico-pathological tumor characteristics. Systemic VEGF levels reduced significantly in the breast cancer patients following tumor excision (p = 0.018). The highest systemic VEGF levels were observed in postmenopausal breast cancer patients. Postmenopausal women who had had a previous hysterectomy had significantly higher VEGF levels than those with an intact postmenopausal uterus (p = 0.001).This study identifies an intact postmenopausal uterus as a potential means of reducing circulating levels of VEGF which could confer a protective effect against breast cancer metastatic potential.Vascular Endothelial Growth Factor (VEGF) is one of the most potent angiogenic cytokines, acting as a specific endothelial mitogen capable of stimulating angiogenesis in vitro and in vivo [1].The adult female reproductive tract, under ovarian steroid hormone influence, is the principle endogenous VEGF producer and the only site where physiological angiogenesis occurs routinely. VEGF ligands and receptors are expressed in the uterine endometrium [2] and myometrium [3] and cyclical variations in serum VEGF during the menstrual cycle have previously been demonstrat