Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery.
BACKGROUND
To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta).


METHODS
We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method.


RESULTS
On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery.


CONCLUSIONS
Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.
Curigliano
G
G
Department of Medicine, Division of Medical Oncology, Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy. guiseppe.curigliano@ieo.it
Petit
J Y
JY
Bertolini
F
F
Colleoni
M
M
Peruzzotti
G
G
de Braud
F
F
Gandini
S
S
Giraldo
A
A
Martella
S
S
Orlando
L
L
Munzone
E
E
Pietri
E
E
Luini
A
A
Goldhirsch
A
A
D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000378:metabolism; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011446:Prospective Studies; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
D016207:Cytokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2