136P Impact of ovarian stimulation on breast tumor biology: First results from a pilot study

The number of cycles of oocyte vitrification for fertility preservation is increasing annually. For young women with breast cancer facing fertility preservation, the impact of ovarian stimulation on tumor biology is unclear. Our pilot study explores this by analyzing breast tumor samples pre- and post-treatment. Ten premenopausal women under 40 years, diagnosed with early-stage breast disease and opting for oocyte cryopreservation, were included. The ovarian stimulation protocol consisted of daily subcutaneous administration of recombinant FSH along with an aromatase inhibitor (AI), with the aim of recruiting multiple follicles without elevation of circulating estradiol levels. Biopsies were collected pre-stimulation and within 24-72 hours post-follicle aspiration and oocytes recovery. Gene expression in formalin-fixed paraffin-embedded tumor samples was analyzed using a 72-gene nCounter panel, encompassing PAM50 subtypes and Risk of Recurrence (ROR) score. Paired SAM with a False Discovery Rate of <5% and t-tests evaluated significant gene expression changes. Baseline pre-treatment PAM50 subtype distribution was 30% Luminal A, 30% Luminal B, 30% HER2-enriched, and 10% Basal-like. Ten of 72 genes (13.9%) showed significant changes, and 12 (16.7%) and 1 (1.4%) gene were altered specifically in patients with Luminal A/B and non-luminal tumors, respectively. The majority of differentially expressed genes (n=10/12; 83.3%) were downregulated post-treatment, including proliferation genes (e.g., CCNB1, CDC6, CENPF, BIRC5, and MYC) and progesterone receptor gene. Two cases showed borderline subtype switches (Luminal A <-> Luminal B). However, no significant shifts were noted in PAM50 ROR scores after treatment. There were no observed correlations with estradiol levels, number of follicles, gonadotropin dosage, or days of stimulation. Ovarian stimulation protocols involving gonadotropin hormones and AI appears biologically safe. The minimal changes observed in tumor biology suggest that this approach does not adversely affect tumor characteristics. However, further studies are necessary.