Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists

Background: Ovarian function suppression (OFS) has emerged as a crucial adjuvant therapy for premenopausal breast cancer patients. Some patients fail to achieve complete OFS with commonly used OFS drugs. The definition of incomplete OFS remains unclear, and large-scale data on its incidence are lacking. This review provides a comprehensive overview of the definition, occurrence, impact on therapeutic efficacy and corresponding treatment measures for incomplete OFS.

Methods: We searched PubMed, Embase and Cochrane Library databases in recent twenty years with keywords as "ovarian function escape", "incomplete OFS" and "estrogen breakthrough", and carried out a snowballing of references to important literature. Clinical literature of premenopausal breast cancer patients treated with OFS was screened. The patient characteristics, definition and incidence of incomplete OFS, prognosis, interventions and other information were extracted.

Results: A total of 17 studies were included in the analysis, including RCTs, retrospective or prospective cohort studies and case reports. Literature indicates that the incidence of incomplete OFS is around 5-50 % when the estradiol (E2) threshold is set as 2.72 pg/mL, 10 pg/mL, 20 pg/mL, or 30 pg/mL. Young age, high body mass index (BMI), and no prior chemotherapy were the risk factors for incomplete OFS. The treatment of incomplete OFS included dose adjustments, alternative OFS drugs, or the adoption of other OFS measures.

Conclusions: The incomplete OFS rate decreased with the extension of treatment time. It is reasonable to monitor E2 levels to ensure successful OFS in the patients with high risk factors for incomplete OFS or with concurrent use of aromatase inhibitor (AI). Transient incomplete OFS seems to have no impact on prognosis, but sustained incomplete OFS needs personalized adjustment of treatment strategy to ensure complete OFS.