The effects of neoadjuvant anastrozole and tamoxifen on circulating vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in breast cancer.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is a key angiogenic factor mediating neovascularization. Soluble VEGF receptor 1 (sVEGFR-1) is an intrinsic negative counterpart of VEGF signaling and the ratio of sVEGFR-1 to VEGF has been shown to be a prognostic factor. Estrogen-bound estrogen receptor enhances VEGF expression, providing a common link between these signaling pathways that may be targeted by endocrine therapy. We investigated the effects of anastrozole and tamoxifen over time on serum VEGF and sVEGFR-1.


METHODS
The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial compared the preoperative use of anastrozole with tamoxifen in postmenopausal women with estrogen receptor-positive primary operable breast cancer over 12 weeks. Circulating VEGF and sVEGFR-1 were measured by ELISA in 106 patients treated with anastrozole or tamoxifen alone at baseline and after 2 and 12 weeks of treatment.


RESULTS
The increase in serum VEGF from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 6% versus 38%; P = 0.047). There was a significant increase in sVEGFR-1 levels after 12 weeks of anastrozole (P = 0.037). The sVEGFR-1/VEGF ratio significantly decreased in the tamoxifen arm (P = 0.013) and the change in sVEGFR-1/VEGF ratio from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 24% increase versus 34% decrease; P = 0.013).


CONCLUSIONS
Treatment with anastrozole and tamoxifen resulted in differential effects on serum angiogenic markers. This may be related to the relative effectiveness of the treatments. These data provide further support for cross talk between estrogen receptor and VEGF.
Banerjee
Susana
S
Breakthrough Breast Cancer Centre, Institute of Cancer Research, London, United Kingdom.
Pancholi
Sunil
S
A'hern
Roger
R
Ghazoui
Zara
Z
Smith
Ian E
IE
Dowsett
Mitch
M
Martin
Lesley-Ann
LA
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; D000077384:Anastrozole; D040281:Vascular Endothelial Growth Factor Receptor-1