Comparison of suboptimal versus adequate ovarian function suppression in premenopausal women with early breast cancer treated with adjuvant endocrine therapy: An exploratory analysis of two prospective studies

PURPOSE: Ovarian function suppression (OFS) combined with tamoxifen or aromatase inhibitor (AI) are standard treatment options for young women with hormone receptor-positive breast cancer. Suboptimal OFS may reduce the efficacy of the endocrine treatment (ET). This study evaluated factors associated with suboptimal OFS induced by gonadotropin-releasing hormone agonist (GnRHa). METHODS: PREFER (NCT02895165) and GIM 23-POSTER (NCT05730647) are multicentric Italian prospective, observational studies enrolling premenopausal women undergoing (neo)adjuvant chemotherapy and/or ET. The present analysis includes only patients enrolled at the coordinating center. Patients receiving ET with OFS were classified into suboptimal (estradiol >25.1 ng/L measured by chemiluminescent immunoassay or resumed menstruation) or adequate OFS. RESULTS: As of June 2024, 488 patients were enrolled (median follow-up: 44.4 months, IQR 20.6-84.0). Of 343 patients receiving adjuvant ET, 315 were in the adequately suppressed group and 28 in the suboptimal suppression group (of whom 55.9 % and 92.9 %, respectively, were receiving an AI). Clinical characteristics (age, BMI, baseline FSH, and estradiol levels) and previous chemotherapy (with or without concurrent GnRHa) showed no association with suboptimal OFS. Concurrent treatment with AI was the only factor significantly associated with suboptimal OFS (HR 12.83, 95 % CI 3.01-54.65; p = 0.001). The proportion of patients with suboptimal suppression was 5.1 % (95 % CI 3.2-8.2) in the first year of ET, rising to 10.5 % (95 % CI 7.1-15.4) within five years. CONCLUSIONS: Approximately 10 % of premenopausal women receiving GnRHa as part of adjuvant ET did not achieve complete OFS. Use of AI was the only factor linked to suboptimal OFS.