Evaluation of Ovarian Function Suppression Failure in Premenopausal Women with Early-Stage Breast Cancer

Background/Objectives: Ovarian function suppression (OFS) is part of endocrine therapy treatment for high-risk premenopausal women with hormone receptor-positive (HR+) breast cancer (BC). Incomplete OFS may occur and compromise treatment efficacy. Methods: We conducted a retrospective single-center cohort study of premenopausal patients with HR + BC treated with OFS therapy at the Centre des maladies du sein (CMS) of the CHU de Québec (Québec, Canada). Ovarian function suppression failure was defined as either biochemical failure (estradiol (E2) levels within the premenopausal range according to local immunoassays used) or clinical failure (return of menstrual bleeding). Patients' characteristics, treatment specifics and side effects, timing and type of OFS failure, recurrence, and mortality were analyzed. Results: Among 208 included patients, 17 (8.2%) experienced at least one episode of OFS failure during a median follow-up of 62.6 months. Most failures occurred early, with 76.2% occurring within the first year of treatment. No significant differences were observed between patients with and without OFS failure regarding age, body mass index (BMI), or prior chemotherapy exposure. Patients with OFS failure had a significantly younger age at first pregnancy and higher rates of active smoking. No BC recurrence or death occurred among patients with OFS failure. Treatment-related side effects were common, and 23.0% of OFS regimens were discontinued due to adverse effects. Conclusions: In this study, OFS failure occurred in fewer than 10% of premenopausal patients. Younger age at first pregnancy and active smoking may be associated with OFS failure, but further data are needed to validate these exploratory associations. These findings reinforce the need for larger prospective studies to better assess OFS failure and develop standardized monitoring strategies to optimize treatment efficacy.