Abstract CT301: Late disease recurrence in estrogen receptor positive (ER+) premenopausal breast cancer (BC)
Authors: Recchia Francesco , Candeloro Giampiero , Necozione Stefano , Rea Silvio , Hoo William Soo , Cantor Tom 
Published: May 2015

Abstract
Background:
BC is often a slowly growing disease. For this reason, in order to establish the validity of a therapeutic approach, we need long term follow up, especially in the adjuvant setting. In addition, estradiol (E2) plays a key role in premenopausal BC growth through the induction of vascular endothelial growth factor (VEGF) and the expansion of T-Regulatory cells (T-Regs). We hypothesized that, decreasing plasma E2, the most important inducer of BC, we could reduce VEGF and, therefore, decrease the recurrence rate in premenopausal patients with high risk breast cancer. After a median follow-up &gt;100 months here we present the results of an adjuvant approach in high-risk premenopausal early breast cancer: Luteinizing hormone releasing hormone (LHRH), tailored chemotherapy, radiation therapy and an aromatase inhibitor in ER+ patients. Primary endpoint of this study was the evaluation of E2 and VEGF; secondary end points were the 5 and 15-year disease-free survival (DFS) and overall survival (OS) rates. Methods: Between June 1997 and June 2007, 200 premenopausal high risk early BC patients were entered into the study. The LH-RH analogue was administered before starting chemotherapy. 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 by an aromatase inhibitor to ER+ patients. 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%). After a median follow-up of 104 months (range 63-180), a statistically significant decrease of E2 (P&lt;0.0001) and VEGF (P&lt;0.0001) were observed. 5-year DFS and OS rate were 89% and 96%, respectively, while the 15-year DFS and OS rate were 62%, and 73%, respectively. ER+ patients had a better DFS (P&lt;0.05) with respect to ER- patients, while no difference was observed in OS. 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 E2 and VEGF and to improve the expected DFS and OS rate in premenopausal high risk ER+ and ER- BC patients, at the price of a moderate toxicity. No recurrence after 5 years was observed in ER- patients who had late new primaries. ER+ patients had recurrences even after 15 years. Long term therapy and new immunologic approaches are being evaluated in premenopausal patients with ER+ tumors.
Citation Format: Francesco Recchia, Giampiero Candeloro, Stefano Necozione, Silvio Rea, William Soo Hoo, Tom Cantor. Late disease recurrence in estrogen receptor positive (ER+) premenopausal breast cancer (BC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT301. doi:10.1158/1538-7445.AM2014-CT301