Abstract GS3-02: Fertility and ovarian function preservation in premenopausal women with early breast cancer: results from the multicenter prospective PREgnancy and FERtility (PREFER) study

Abstract Background: Oncofertility counseling is standard of care in premenopausal patients (pts) with early breast cancer (EBC) who are candidates to receive chemotherapy (CT). However, limited data exist on the uptake of ovarian function and/or fertility preservation strategies and reasons for refusal. Moreover, for pts undergoing controlled ovarian stimulation (COS) for gamete cryopreservation, the evidence on its safety derives mostly from retrospective studies; thus, some physicians remain concerned in offering this strategy. To address the significant challenges of the oncofertility counseling in premenopausal women with EBC, the PREFER study was developed as a national comprehensive program aiming to optimize care and improve knowledge in this field. Methods: PREFER (NCT02895165) is a multicenter prospective cohort study conducted in 23 Italian centers affiliated to the Gruppo Italiano Mammella (GIM) study group. Eligible pts were premenopausal women aged <=45 years at diagnosis of EBC. Before starting (neo)adjuvant CT, a proper oncofertility counseling was offered. Pts aged <=40 years were offered oocyte cryopreservation (OC; embryo cryopreservation is forbidden by law in Italy) and/or ovarian tissue cryopreservation (OTC) for preserving fertility, as well as the use of a gonadotropin-releasing hormone agonist (GnRHa) during CT for ovarian function preservation. Pts aged 41-45 years were only offered the use of a GnRHa during CT for ovarian function preservation. Universal coverage of all these procedures is provided by the Italian National Health System. The primary objective was to assess the acceptance rates of these strategies and reasons for refusal. Assessing the safety of COS for OC in terms of disease-free survival (DFS) and overall survival (OS) was a secondary objective. Results: Between November 2012 and December 2024, 746 pts were enrolled, of whom 533 were aged <=40 years and 213 between 41-45 years. Median age was 38 years (IQR 34-41 years); 537 (72.0%) pts had hormone receptor-positive EBC and 93 (12.5%) were germline BRCA carriers. Among pts aged 41-45 years, 160 (75.1%) accepted use of a GnRHa during CT. Main reasons for refusal were completion of family planning in 24 (11.3 %) pts. Among pts aged <=40 years, 476 (89.3%) accepted use of a GnRHa during CT. Main reason for refusal was completion of family planning in 18 (3.4%) pts. A cryopreservation technique was accepted by 133 (25.0%) pts, of whom 127 (23.8%) underwent OC and 6 (1.1%) OTC. Main factors associated with acceptance of these strategies were younger age at diagnosis (OR 0.80; 95% CI 0.76-0.85 for 1-year increase), no prior children (OR 0.08; 95% CI 0.04-0.13), more recent year at EBC diagnosis (OR 1.37; 95% CI 0.74-2.51 for 2016-2020 vs. 2012-2015; OR 2.06; 95% CI 1.15-3.67 for 2021-2024 vs. 2012-2015) and lower tumor grade (OR 0.55; 95% CI 0.36-0.85 for G3 vs. G1-2). No difference in acceptance of these strategies according to hormone receptor status, BRCA status, timing of CT administration, tumor size and nodal status was observed. Median follow-up was 3.8 years (IQR 1.7-6.6 years). Undergoing COS for OC was not associated with any detrimental effect on DFS (adjusted HR 0.78; 95% CI 0.27-2.26) nor on OS (adjusted HR 0.53; 95% CI 0.06-4.73). Conclusions: PREFER is the largest multicenter prospective cohort study addressing oncofertility care in premenopausal women with EBC. Most pts (89.3% of those <=40 years and 75.1% of those 41-45 years) accepted a GnRHa during CT for ovarian function preservation. One out of four (25.0%) pts aged <=40 years accepted to undergo cryopreservation procedures (mainly OC). COS for OC did not appear to negatively influence prognosis. These results provide novel prospective evidence to improve the oncofertility counseling of premenopausal women with EBC. Citation Format: M. Lambertini, E. Blondeaux, V. Fontana, S. Cinieri, I. Paris, A. Vandone, C. Andreetta, V. Sini, I. Meattini, C. Bengala, M. Dieci, L. Livraghi, R. Cioffi, D. Bilancia, F. Sottotetti, S. Mura, A. Denaro, D. Favero, G. Arpino, F. Poggio, M. Razeti, E. Chiappe, F. Bruzzone, L. Arecco, C. Massarotti, P. Vanella, F. Pavese, L. Orlando, F. Puglisi, P. Anserini, L. Boni, L. Del Mastro. Fertility and ovarian function preservation in premenopausal women with early breast cancer: results from the multicenter prospective PREgnancy and FERtility (PREFER) study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS3-02.