Abstract 3722: Ovarian suppression with gonadotropin-releasing hormone analogues (Gn-RH) in high risk premenopausal breast cancer patients (PM-HR-BC): decrease of T regulatory cells (T-regs) and of vascular endothelial growth factor (VEGF)

Abstract

Abstract Background: In a previous phase II study we have shown an improvement of disease-free survival and overall survival of 180 premenopauseal high-risk early breast cancer patients (PM-HR-BC) treated with ovarian suppression with Gn-RH and a chemotherapy tailored to the peculiar clinical situation. Aim of this study was the evaluation of VEGF and T-regs in a group of PM-HR-BC patients treated with the above mentioned therapy. Methods: From 01/2006 to 12/2008 54 patients with PM-HR-BC were entered into this study. At baseline, one week before chemotherapy, patients received a Gn-RH analogue which was continued for five years. Tailored adjuvant chemotherapy, included anthracycline and taxane based regimens. 11 patients with triple negative tumors, received a platinum-based consolidation high-dose chemotherapy with (n. 7) or without (n. 4) autologous peripheral blood progenitor cell transplantation, respectively. Radiation therapy was administered to all patients that had received breast conserving surgery. Patients received a strong psychological support, biphosphonates, and after the end of chemotherapy, estrogen receptor positive (ER+) patients received an aromatase inhibitor. Results: Characteristics of patients. Median age was 41 years (range, 26-44 yrs). 79% of patients were ER+, while 21% were estrogen receptor negative. Total number of positive nodes was 145, with a mean of 2,7 for each patient (range 0-25). G3 tumors were observed in 33% of patients, C-erB-2 status (FISH) was positive in 17% of patients, while mean Ki-67 value was 27%. Serum estradiol was suppressed to values < 40 pg/mL in all patients. After six months and one year, a statistically significant decrease was observed in T-regs number (p< 0.005) and VEGF (p< 0.005) with respect to baseline values. No impairement of cognitive function was observed with respect to baseline conditions. After a median follow-up of 26 months, 4 years progression-free survival and overall survival rate were 97% and 100%, respectively. Conclusions: These data show that ovarian suppression with a Gn-RH analogue decreases T-regs and VEGF, and seems to improve the expected outcome of PM-HR-BC patients through immunologic mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3722.