Ovarian Escape in Hormone Receptor-Positive Breast Cancer: Mechanisms, Risk Factors, Clinical Consequences, and Management Strategies

Abstract: Ovarian function suppression (OFS) is essential in the treatment of premenopausal patients with hormone receptor-positive breast cancer. However, during therapy with gonadotropin-releasing hormone analogs (GnRHa), some patients may experience a phenomenon known as “ovarian escape” in which levels of gonadotropins and estradiol return to premenopausal ranges, indicating partial or complete recovery of ovarian function. This phenomenon may markedly compromise the efficacy of endocrine therapy and increase the risk of breast cancer recurrence and disease progression. At present, there is no universally accepted or standardized definition for “ovarian escape” nor are there recognized diagnostic criteria. In clinical research, a serum estradiol threshold of 2.72 pg/mL is frequently employed as a reference standard for effective OFS. Systematic reviews have shown that different studies report varying incidence rates, diagnostic methods, and interpretations regarding its clinical significance, further adding to the complexity of this issue. Therefore, this review aims to systematically analyze key topics related to “ovarian escape” including its underlying mechanisms, potential risk factors, clinical consequences, and feasible management strategies, with the goal of providing scientific evidence and guidance for clinical practice. Keywords: breast cancer, ovarian function suppression, ovarian escape