This is a multicenter, prospective, randomized controlled, phase II study. The primary objective is to evaluate the effect of endocrine therapy modification (switching from a 3-month to a 1-month GnRHa) versus continuation of the 3-month GnRHa on E2 control at 3 months in young patients with hormone receptor-positive breast cancer and iOFS.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
1-month GnRH (goserelin 3.6 mg depot or goserelin 3.6 mg implant or leuprolide 3.75 mg depot) +endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)
3-month GnRH (goserelin 10.8 mg implant or leuprolide 11.25 mg depot) + endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)
Proportion of Participants with E2 <30 pg/mL at 3 Months
The primary endpoint is defined as the proportion of patients with E2 \<30 pg/mL at 3 months, comparing patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy.
Time frame: 3 months post randomization
Proportion of patients with E2 <30 pg/mL at 6 months after randomization
This endpoint is defined as the proportion of patients with E2 \<30 pg/mL at 6 months, comparing patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy.
Time frame: 6 months post randomization
Time to adequate ovarian function suppression
This endpoint is defined as the time from the first occurrence of iOFS to the first measurement of E2 \<30 pg/mL.
Time frame: Assessed over a period of up to 12 months following randomization
Patient Age
Age of participants at the time of randomization, categorized by iOFS status (Persistent vs. Transient).
Time frame: At randomization
3-year invasive disease-free survival in patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy
Invasive disease-free survival is defined as the time from randomization to the first occurrence of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause.
Time frame: From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
3-year invasive disease-free survival in patients with persistent iOFS and those with transient iOFS
Time frame: From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
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Intraclass Correlation Coefficient (ICC) for the Consistency of the SEMS Method
The consistency of the SEMS method will be assessed by calculating the Intraclass Correlation Coefficient (ICC) between GnRHa 1M and GnRHa 1M at the post-assay time point.
Time frame: post SEMS assay
Adverse events
Adverse events will be graded according to the NCI-CTCAE Version 5.0.
Time frame: From the date of treatment initiation until the date of disease progression, intolerable toxicities, death, withdrawal of consent, or completion of planned 3-year postoperative follow-up, whichever occurred first