Ovarian suppression in adjuvant hormone therapy for breast cancer: research and perspectives

Background. Hormone receptor-positive (HR+) disease represents the predominant subtype of HER2-negative breast cancer, and adjuvant endocrine therapy (AET) with tamoxifen or aromatase inhibitors (AI) remains its therapeutic cornerstone. In premenopausal women, ovarian suppression (OS) – achieved reversibly with GnRH agonists (triptorelin, goserelin, buserelin, leuprorelin) or irreversibly by oophorectomy – constitutes an essential component of AET, either as a monotherapy adjunct or as a mandatory partner for AI administration. Early evidence, including the 1995 EBCTCG meta-analysis and subsequent trials (IBCSG 11–93, INT 0101, ZIPP, ABCSG‑12), produced conflicting results, leading to divergent international guideline recommendations by 2013.
Methods. This review synthesizes historical and contemporary evidence on the role of OS in AET, focusing on the pivotal SOFT and TEXT trials and their long-term follow-up, alongside real-world and meta-analytic data on GnRH agonist dosing schedules.
Results. Final 15-year SOFT trial results demonstrated significant disease-free and overall survival benefit from OS in high-risk premenopausal patients, particularly those remaining premenopausal after chemotherapy and women under 35 years (15-year breast cancer-free interval: 73.5 % with exemestane+OS versus 70.5% with tamoxifen+OS versus 67.0% with tamoxifen alone; in patients<35 years, 69.6% versus 64.1% versus 51.3%, respectively). Combined TEXT and SOFT data corroborated these findings. The SOFT-EST substudy revealed suboptimal estradiol suppression in 34% of patients receiving exemestane plus triptorelin. The 10-year ASTRRA update and the 2026 EBCTCG meta-analysis (23 RCTs, 18,851 patients) confirmed significant reductions in recurrence and breast cancer mortality with OS, especially in women under 45. Comparative data indicate equivalent efficacy between monthly and 3-monthly GnRH agonist regimens, with 3-monthly dosing associated with improved adherence and tolerability.
Conclusion. Cumulative long-term evidence firmly establishes OS as indispensable in AET for high-risk premenopausal HR+ early breast cancer, with 3-monthly GnRH agonist triptorelin, recently registered in Russia, offering equivalent efficacy and enhanced practicality for routine clinical use.

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