Abstract P2-08-09: Predictors of inadequate ovarian function suppression (OFS) in premenopausal women with hormone receptor (HR)-positive breast cancer receiving a gonadotropin-releasing hormone (GnRH) agonist in combination with endocrine therapy

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Abstract Background: In premenopausal women with early-stage hormone receptor (HR)-positive breast cancer and a higher risk of recurrence, the addition of ovarian function suppression (OFS) to endocrine therapy has been shown to improve disease outcomes, as demonstrated by combined analysis of the SOFT/TEXT trials. Estradiol (E2) is the primary source of estrogen in premenopausal women and is synthesized from the ovaries through indirect control of gonadotropin-releasing hormone (GnRH). Endocrine therapy with a GnRH agonist has become a mainstay of treatment in premenopausal women for ovarian suppression. However, studies have shown that up to 25% of patients do not achieve adequate ovarian suppression within the first year of treatment. Data remains limited regarding whether monitoring of OFS should routinely be performed and is not part of current NCCN guidelines. The aim of our study was to evaluate premenopausal women in a ‘real world’ setting at our institution who did not achieve adequate OFS and to assess potential contributing factors. Methods: This was a retrospective, descriptive study of premenopausal women ≥18 years of age at our institution from 2020-2022 with stage I-III HR-positive breast cancer receiving OFS in combination with endocrine therapy with either an aromatase inhibitor or tamoxifen. OFS was achieved by use of a GnRH agonist with leuprolide or goserelin. Patients who had two or more consecutive tests showing non-suppressed estradiol levels (E2 level >20 pg/mL) were considered to have inadequate ovarian suppression. Data regarding patient age at the start of treatment, BMI, receipt of neoadjuvant and/or adjuvant chemotherapy, history of prior pregnancies, history of diabetes mellitus, and choice of initial GnRH agonist were examined. The rate of change to another GnRH agonist upon ovarian suppression failure was also determined. Results: Twenty-six patients (age range: 27-50) were identified at our institution who received either leuprolide or goserelin. Of these patients, 25 received OFS every month (96%) and 1 received OFS every three months (4%). The rate of inadequate OFS among all patients was 30.8%. The average age at the start of treatment was 40.1 years for those with adequate OFS compared to 37.9 years for those with inadequate OFS. Average BMI was 26.7 in the adequate OFS group and 30.3 in the inadequate OFS group. In the adequate OFS vs. inadequate OFS group, 17% vs. 38% had received neoadjuvant chemotherapy, and 39% vs. 63% had received adjuvant chemotherapy, respectively. 17% of patients in the adequate OFS group had a history of diabetes mellitus, compared to 25% in the inadequate OFS group. In the adequate OFS versus inadequate OFS group, 33% versus 50% had a history of at least one term pregnancy, respectively. For those who received leuprolide initially, 67% had adequate OFS. In comparison, for those who received goserelin initially, 33% had adequate OFS. Among the patients with inadequate OFS, 50% had their treatment subsequently changed to the alternative GnRH agonist. Discussion: This study showed that inadequate OFS was detected in 31% of the patients, half of whom underwent a subsequent change in therapy to the alternative GnRH agonist. Patients who received leuprolide initially were more likely to have adequate OFS compared to those who received goserelin. A higher BMI, history of diabetes, and history of term pregnancy were found in patients with inadequate OFS. Further research is needed to establish monitoring guidelines for estradiol and the optimal degree of ovarian suppression for premenopausal patients receiving OFS. Citation Format: Maryann Kwa, Leyla Bayat, Nancy Chan, Arturo Orlacchio, Cigdem Karayigitoglu, Doaa Ayoubi, Tsivia Hochman, Douglas Marks. Predictors of inadequate ovarian function suppression (OFS) in premenopausal women with hormone receptor (HR)-positive breast cancer receiving a gonadotropin-releasing hormone (GnRH) agonist in combination with endocrine therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-08-09.

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