Changes in plasma vascular endothelial growth factor, angiopoietins, and their receptors following surgery for breast cancer.
BACKGROUND
Vascular endothelial growth factor (VEGF), a major angiogenic growth factor, is involved in the pathogenesis of cancer. Plasma VEGF is raised in breast cancer and falls after successful surgery. Less is known about angiopoietins 1 and 2 (Ang-1, Ang-2). All three growth factors act on cells via receptors; Flt-1 for VEGF and Tie-2 for the angiopoietins. Cancer is also marked by abnormalities in platelet activation (marked by soluble P selectin) and inflammation (interleukin-6 [IL6]). We hypothesised altered plasma Ang-1, Ang-2, Flt-1 and Tie-2 in breast cancer that would normalize after 3 and 12 months treatment (i.e., surgery plus chemo/radiotherapy).


METHODS
Baseline venous blood was obtained from 40 women with breast cancer and 30 age-matched women with benign breast disease (BBD) also requiring surgery. Samples were taken again 3 months and 1 year later. Soluble P selectin, IL6, VEGF, Ang-1, Ang-2, Flt-1 and Tie-2 were measured in citrated plasma by ELISA.


RESULTS
Women with breast cancer had raised VEGF (7-fold), Ang-1 (50% higher) and Tie-2 (2-fold), but lower Flt-1 (to 26%), compared to the BBD women that broadly correlated with markers of platelet activation and inflammation. A level of Tie-2 or VEGF >95th percentile of the BBD group correctly identified 68% and 52% of the women with breast cancer. After 3 months of treatment, VEGF and Ang-1 normalized (as did IL6 and soluble P selectin) but Tie-2 was significantly lower only after 1 year. There were no significant changes in the women with BBD.


CONCLUSIONS
Treatment for breast cancer (surgery followed by chemotherapy and/or radiotherapy) is effective in reducing plasma VEGF, Tie-2 and Ang-1. These may be linked pathogenically with coagulation and inflammation.
Caine
Graham J
GJ
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, United Kingdom.
Stonelake
Paul S
PS
Lip
Gregory Y H
GY
Blann
Andrew D
AD
D000368:Aged; D042682:Angiopoietins / Q000097:blood*; D001941:Breast Diseases / Q000097:blood / Q000601:surgery; D001943:Breast Neoplasms / Q000097:blood / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D042787:Receptor, TIE-2 / Q000097:blood*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D042682:Angiopoietins; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor