Abstract P6-09-06: Estrogen (E2) suppression following diagnosis of node positive (N+) breast cancer (BC) in premenopause. Long term follow-up of a phase II study

Abstract

Abstract Background: E2 plays a key role in human reproduction and in premenopausal BC growth through the induction of vascular endothelial growth factor (VEGF) and the expansion of T-Regulatory cells (T-Regs). In addition, few clinical data exist on long-term outcome of high-risk N+ premenopausal BC treated with E2 deprivation, by luteinizing hormone releasing hormone (LH-RH). We hypothesized that E2 suppression, following diagnosis of N+ BC in young premenopausal patients, could decrease VEGF and T-Regs and, therefore, could reduce the recurrence rate. Primary endpoint of this study was the evaluation of T-Regs and VEGF of premenopausal patients with high-risk N+, estrogen receptor positive (ER+) and negative (ER-) early BC, treated with an LH-RH analogue. Secondary endpoints were the 10 and 15-year disease-free survival (DFS) and overall survival (OS) rates. Methods: Between 06-1997 and 06-2007, 200 premenopausal high risk early BC patients were entered into the study. Before starting chemotherapy, the LH-RH analogue was administered, 3.75 mg every 28 days for 1 year to the first 64 patients. The same monthly dose was given, for 2 years, to 36 patients. Having observed a decrease of 31% in the recurrence rate for the longer administration of LH-RH analogue, we gave the 11.25 mg dose every 84 days, for 5 years, to the remaining 100 patients. Breast conserving and radical surgery were performed in 74% and 26% of patients, respectively. Systemic therapy was tailored to the biological characteristics of each patient and followed by radiation therapy, and hormonal therapy in ER+ tumors. Results: Median patient's age was 43 years (range 26-45). Mean number of positive axillary nodes was 3.2 (range 1-25). 71% of patients were ER+ and/or progesterone receptor (PGR+), 29% were ER - and PGR-. Median KI-67 was 30% (range 15% -100%). 21% of patients were c-ErbB-2 positive and 11 of them were treated with trastuzumab for 1 year. After a median follow up of 102 months (range 60-180), a statistically significant decrease of VEGF and T-Regs was observed, both in ER+ (P<0.0001) and ER- patients (P<0.0001). Ten-year DFS and OS rate were 86% and 90%, respectively, while the 15-year DFS and OS rate were 62%, and 73%, respectively. Two c-ErbB-2 positive patients (4.7%), had disease recurrence. ER+ patients had a better DFS (P<0.05) and OS (P<0.0001) with respect to ER- patients. The standard pattern of toxicity of chemotherapy was observed, while hot flashes and G1 osteopenia occurred after LH-RH analogue administration. Conclusions: E2 deprivation with an LH-RH analogue is able to decrease plasma VEGF and T-Regs in premenopausal high risk ER+ and ER- BC patients, at the price of a mild toxicity. A favourable impact on DFS and OS was observed. ER- patients had late new primaries, but no recurrence after 5 years, while ER+ patients had disease recurrence even after 15 years. Long term therapy should have further evaluation in premenopausal patients with ER+ tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-06.