Abstract 5055: The role of estrogens and vascular endothelial growth factor (VEGF) in premenopausal breast cancer carginogenesis and disease progression

Abstract

Abstract Background. Estrogen is important in breast cancer development and there is evidence in vitro, that it modulates VEGF expression in breast cancer cells through transcriptional activation. However few clinical studies have investigated the association between VEGF and estrogens in humans. Objective of this study was to evaluate weather estrogen suppression with an LH-RH analogue was able to downregulate VEGF expression, and thus decrease its plasma concentration, in premenopausal patients with high-risk early breast cancer. Patients and methods: From April 2003 to October 2008 we conducted this study on 100 premenopausal early breast cancer patients. At baseline, after surgery, before any type of therapy, plasma VEGF and sex hormones (estradiol, progesterone, FSH, LH) were evaluated. Evaluation was repeated each year. Patients received an LH-RH analogue for 5 years, a chemotherapy that was tailored to the biological characteristics of each patient, radiation therapy, and hormonal therapy in estrogen receptor positive (ER+) tumors. Primary end point was the evaluation of VEGF. Secondary end points were progression-free survival (PFS) and overall survival (OS). Results: Median age was 43 years (range 26-45); mean number of positive axillary nodes was 3.3. (Range 0-25). Fifty-three patients were ER+ and progesterone receptor positive (PGR+), 17 were ER negative (−) and PGR-, 30 were ER+ and PGR-, Median KI-67 was 33% (range 15%-100%). Twenty patients were Herb-2 positive by FISH. A statistically significant decrease of VEGF was observed after 1 year. At 5 years and during the study period, plasma VEGF continued to decrease (p<0.001) in 94% of patients that were disease-free, while in 6% of patients with disease relapse, VEGF increased with respect to baseline values. No unexpected toxicity of chemotherapy was observed, while hot flashes and G1 osteopenia occurred after LH-RH analogues administration. After a median follow-up of 50 months (range 24-90), 8-year disease free survival and overall survival rated were 94% and 100%, respectively. Conclusion: Estrogen deprivation with an LH-RH analogue is able to decrease plasma VEGF levels in premenopausal high risk breast cancer patients. These data show how estrogens, through VEGF modulation, may be responsible for the worst prognosis that is observed in premenopausal breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5055. doi:10.1158/1538-7445.AM2011-5055