The effect of menopause and hysterectomy on systemic vascular endothelial growth factor in women undergoing surgery for breast cancer.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine produced physiologically by the uterus. Pathological secretion by tumours promotes growth and metastasis. High circulating VEGF levels potentially have a deleterious effect on breast cancer by promoting disease progression. 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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Lowery
Aoife J
AJ
Department of Surgery, Clinical Science Institute, University College Hospital Galway, Galway, Ireland. aoife.lowery@gmail.com
Sweeney
Karl J
KJ
Molloy
Alan P
AP
Hennessy
Emer
E
Curran
Catherine
C
Kerin
Michael J
MJ
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000097:blood / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007044:Hysterectomy; D007986:Luteinizing Hormone / Q000097:blood; D008593:Menopause; D008875:Middle Aged; D009367:Neoplasm Staging; D011374:Progesterone / Q000097:blood; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D004967:Estrogens; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone