Impact of Formulation Change on Ovarian Suppression in Young Breast Cancer Patients.

In China, breast cancer occurs at a young age, with a peak incidence at 40-49 years; patients aged ≤45 years account for 20%-24% of cases, and this proportion is increasing. Ovarian function suppression (OFS) combined with aromatase inhibitor (AI) or tamoxifen (TAM), with or without CDK4/6 inhibitors, has become a preferred adjuvant endocrine therapy for intermediate to high-risk premenopausal hormone receptor-positive (HR+) patients with HR+ breast cancer. AI is effective in premenopausal women only when ovarian estrogen production is suppressed, which can be achieved with GnRH agonists (GnRHa). The 3-month GnRHa formulation is commonly preferred in the real world due to its convenience and reduced injection frequency; however, its effectiveness compared with the 1-month formulation remains a concern. Among premenopausal patients receiving GnRHa combined with AI or TAM, approximately 8% experience incomplete ovarian function suppression (iOFS, E2 ≥30 pg/mL). Persistent iOFS may reduce the efficacy of endocrine therapy and potentially increase the risk of disease recurrence. Current clinical guidelines recommend monitoring serum estradiol (E2) levels during GnRHa treatment and suggest potential management strategies, including switching GnRHa formulations from 3-month to 1-month or modifying endocrine therapy (e.g., AI to TAM). However, evidence supporting these strategies is largely derived from retrospective studies or small case series, and prospective data remain limited. This multicenter, prospective, randomized, phase II study is designed to evaluate whether switching from a 3-month to a 1-month GnRHa can reduce E2 levels to \<30 pg/mL within 3 months in premenopausal HR+ young breast cancer patients with iOFS. This study will also assess the long-term efficacy and safety of this strategy.