Abstract PO4-11-10: Comparison of frozen embryo transfer cycle (FET) outcomes between young women with breast cancer (YWBC) with and without pathogenic variants (PV), and breast cancer-free PV carriers
Authors: Sharon-Weiner Maya , Kauffman Amanda , Tanen Adina , Yee Samantha , Madjunkova Svetlana , Glass Karen 
Published: May 2024

Abstract
BACKGROUND: In vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) and monogenic disorders (PGT-M) are valuable tools for YWBC with or without PV such as BRCA1/2, ATM, CHEK2, PMS2 to prevent variant transmission to offspring.  However, to date, there is scarce data on the usability of these cryopreserved, tested embryos and on the outcomes of FET cycles within the cancer population. It has been suggested that PV may influence endometrial thickness which is associated with embryo implantation and ultimately FET success rates. Thus, this study aimed to compare reproductive outcomes of FET cycles between YWBC with an identified PV, breast cancer (BC) patients without a PV, and cancer-free PV-carriers who returned to use their cryopreserved oocytes or embryos derived from IVF ± PGT-A/M cycles.
METHODS: Patients that underwent either fertility preservation (FP) prior to BC therapy or preventative IVF/PGT-A/M cycles from 2009-2023 were included. All IVF & PGT-A/M was performed at academic IVF centre. Genetic testing was conducted using high resolution next generation sequencing on the Illumina platform. We compared reproductive outcomes between 3 groups: 1) YWBC with a known PV (BCPV), 2) YWBC without a PV (BCNV), 3) Cancer-free patients who had a PV (CFPV). Primary outcomes measured were endometrial thickness, and FET success rates (i.e., ongoing pregnancy or live birth) analyzed by chi-square, t-tests and ANOVA.
RESULTS: 185 patients underwent 202 cycles for either oocyte or embryo freezing.
Mean age was 33.8±4.6 years (range 21-45) and mean BMI was 24.6±5.0 kg/m2 (range 15.7-42.7). 64 patients had a PV including BRCA1 (n=22), BRCA2 (n=20) and others (n=22): ATM, BARD1, BRIP1, CHEK2, MLH1, P53, PALB2, PDL2, PMS2, PTCH1, & RAD51D.
When comparing the BCPV, BCNV & CFPV groups, no significant differences were found in the mean age (33.7 ± 4.9 vs. 36.8 ± 4.3 vs. 34.3 ± 4.4 years, p=0.52), mean BMI (26.2 ± 4.9 vs. 24.3 ± 4.8 vs. 24.3 ± 4.8 kg/m2, p=0.13), and the proportion of smokers (23.1% vs. 35.0% vs. 36.4%, p=0.72). Only 60% of BCNV performed PGT-A due to their lack of PV.
As of June 2023, 44 patients (12 in BCPV, 20 in BCNV, and 12 in CFPV) returned to undergo 81 FET cycles (range 1-5/patient). 12/81(14.8%) FETs involved a surrogate. When comparing the BCPV, BCNV & CFPV who had FET, a significant difference was found in the mean age at oocyte retrieval between BCPV & BCNV (32.9±4.4 vs. 37.0±4.0 years, p=0.001) but not with CFPV (33.5±4.4 years). The endometrial thickness at the time of FET between the BCPV, BCNV, and CFPV groups was similar (10.2±1.6 vs. 10.6±2.6 vs. 9.3±1.9 mm, p=0.12), as was the proportion of smokers (25.0% vs. 36.8% vs. 33.3%, p=0.79). YWBC had a mean delay from egg retrieval to their first FET of 37 months. Estrogen receptor positive (ER+) YWBC had a longer delay than ER- patients (40.1±23.8 months vs. 29.6±11.6 months, p=0.25).
29/44 (65.9%) had at least one successful FET and another 5 YWBC conceived naturally or with intrauterine insemination (IUI); the cumulative pregnancy rate was 77.3% (34/44). The clinical pregnancy rate of 81 FETs was 44.4%. The BCPV group (73.7%) had a significantly higher successful outcome than the BCNV (35.3%) and CFPV (35.7%) groups (p=0.01).
CONCLUSIONS: FP done at the time of a BC diagnosis is an effective tool to preserve fertility potential. 77% of patients had at least one baby from either IVF, IUI or conceived naturally. We did not find a difference in endometrial thickness in PV carriers. While all YWBC had a delay to their first FET from the time of their retrieval, those who were ER+ had a longer delay than ER- because of their need for endocrine therapy. The BCPV group had the highest FET success rate which is likely due to their younger age and use of PGT-A/M thereby eliminating FETs of abnormal embryos that would fail to implant. The BCNV were older with more untested embryos. The CFPV group transferred euploid embryos and thus the lower success rate is puzzling and needs further investigation.
Citation Format: Maya Sharon-Weiner, Amanda Kauffman, Adina Tanen, Samantha Yee, Svetlana Madjunkova, Karen Glass. Comparison of frozen embryo transfer cycle (FET) outcomes between young women with breast cancer (YWBC) with and without pathogenic variants (PV), and breast cancer-free PV carriers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-10.