Abstract PS13-03: Fertility preservation for breast cancer patients before chemotherapy

Abstract

Abstract Background: Various strategies of fertility preservation for breast cancer patients have been purposed for women at childbearing age. Ovarian stimulation protocols for oocyte/embryo cryopreservation are common means, but are introduced differently and detail regimens vary widely. Protocols for better oocyte cryopreservation outcomes and patients’ hormone stability remain to be determined. Research Objectives and Rationale: To compare oocyte/embryo cryopreservation outcomes after random-start ovarian stimulations with conventional ones as well as to investigate the effects after double ovarian stimulation cycles, co-administration of aromatase inhibitors or tamoxifen on stabilizing breast cancer patients’ estrogen level, the efficiency of oocyte in vitro maturation for fertilization and the impact of patients' genetic background on fertility preservation outcomes. Methods: A systematic review followed by a meta-analysis was performed to identify all relevant studies published before June 2020. The primary outcomes were the numbers of retrieved oocytes. The secondary outcomes were the numbers of mature oocytes and peak serum estradiol levels. Outcomes: A total of 29 studies met the inclusion criteria. Random-start ovarian stimulations resulted in comparable numbers of retrieved oocytes as conventional protocols did (retrieved oocytes: 503 patients, weighted mean difference [WMD]: -0.01, 95% CI: -2.08 - 2.06, P = 0.99; I2= 0%). Two cycles of ovarian stimulation have significant higher numbers of total retrieved oocytes compared to a single cycle (102 patients, WMD: 7.91, 95% CI: 3.42 -12.40, P = 0.0006; I2= 0%). Both co-administration of letrozole and tamoxifen showed similar results of retrieved oocytes compared to those without (letrozole versus without: 681 patients, WMD: -0.68, 95% CI: -1.96 - 0.61, P = 0.30; I2= 0%) (tamoxifen versus without: 87 patients, WMD: 0.67, 95% CI: -1.29 - 2.64, P = 0.50; I2= 45%). Significant lower peak serum estradiol level was observed in letrozole-based groups compared to letrozole-free groups (301 patients, WMD: -1.05, 95% CI: -1.21 - -0.89, P < 0.00001; I2= 0%). No significant differences were found in peak serum estradiol level between those co-treated with tamoxifen and those without (87 patients, WMD: 0.21, 95% CI: -0.01 - 0.43, P = 0.07; I2= 26%). Regarding breast cancer patients with different BRCA gene background, lower AMH levels were discovered in those with BRCA mutations (831 patients, WMD: -0.63, 95% CI: -1.18 - -0.08, P = 0.03; I2= 47%); however, no significant differences were found in the numbers of retrieved oocytes (retrieved oocytes: 550 patients, WMD: -1.33, 95% CI: -2.72 - 0.05, P = 0.06; I2= 0%). Wider implications: We systematically investigated various aspects of ovarian stimulation for oocyte retrieval in breast cancer patients undergoing fertility preservation prior to chemotherapy, our review indicated that (1) random-start controlled ovarian stimulation protocol showed comparable oocyte yields with minimal delays of referral to initiate ovarian stimulation; (2) two ovarian stimulation cycles results in higher numbers of retrieved oocytes while back-to-back and conventional two cycles showed no significant differences; (3) combinations with letrozole demonstrated a safer way over tamoxifen and anastrozole in terms of lowering estradiol level during stimulation processes; (4) in vitro maturation of immature oocytes can maximize the numbers of oocytes for cryopreservation; and (5) regarding patients’ genetic backgrounds, those with BRCA mutations have lower AMH levels, but similar in numbers of retrieved oocytes to those without BRCA mutations. Nonetheless, we look forward to higher evidence-level studies to understand the clinical relevance of these protocols for ovarian stimulation in breast cancer patients desiring fertility preservation before chemotherapy. Citation Format: Chih-Ning Chen, Lu-Te Chang, Ka-Wai Tam. Fertility preservation for breast cancer patients before chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-03.