Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions

We hypothesized that the regulation of microvascular functions and angiogen esis in breast tissue, a well known target of ovarian steroid action, is de pendent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjac ent non-neoplastic breast tissue of 19 breast cancer patients by quantitati ve reverse transcriptase polymerase chain reaction. In non-neoplastic breas t specimens the expression levels of all detected VEGF-A-isoforms (189, 165 , 121) were significantly higher in premenopausal compared to post-menopaus al women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influ ence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to b reast cancer tissue, appears to be hormonally dependent. Endogenous and the rapeutically used hormonal steroids might, therefore, cause clinically rele vant changes of the angiogenic phenotype of the human breast. (C) 1999 Canc er Research Campaign.