The study shows that in premenopausal breast‑cancer patients on the GnRH agonist triptorelin, about one‑fifth don’t get full ovarian suppression as measured by estradiol (E2) levels. Regular E2 testing (monthly) can spot this, and switching to a different GnRH agonist can restore suppression in roughly half the cases. This suggests that hormone‑blocking protocols need routine hormone checks and flexibility in drug choice.

Breast cancer is the most common malignancy among females. The Tamoxifen and Exemestane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT) were two landmark studies, which showed adjuvant therapy with the aromatase inhibitor (AI), exemestane, or tamoxifen combined with ovarian function suppression (OFS) improved disease-free survival (DFS) among premenopausal women (Pagani et al. in N Engl J Med 371(2):107-118, 2014). However, data has since emerged regarding incomplete OFS with Gonadotropin-releasing hormone (GnRH) agonists in some premenopausal patients. The SOFT Estrogen Substudy (SOFT-EST) was a prospective substudy of SOFT, which evaluated estradiol (E2) levels to determine if patients on exemestane and triptorelin experienced suboptimal ovarian function suppression. In this study, 17% of patients had an E2 level greater than 2.72 pg/mL at each time point, which was determined to be incomplete OFS. This study called into question whether E2 levels should routinely be monitored in women on GnRH agonists (Bellet et al. in J Clin Oncol 34(14):1584-1593, 2016). The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) provide recommendations to monitor E2 levels in premenopausal patients on an aromatase inhibitor (AI) due to the concern of incomplete OFS for patients receiving GnRH agonist therapy (Burstein et al. in J Clin Oncol 37(5):423-438, 2019, National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2024. www.nccn.org ). The purpose of our study is to develop and implement a protocol for monitoring E2 levels at Froedtert & MCW based on the NCCN and ASCO recommendations. This study implemented an OFS monitoring guideline in combination with a collaborative practice agreement at Froedtert & MCW. Pharmacists were responsible for ordering and monitoring E2 levels monthly on eligible patients based on a specified protocol. An E2 level ≤ 2.72 pg/mL while receiving an AI or ≤ 21 pg/mL while receiving tamoxifen in addition to a GnRH agonist injection was defined as complete OFS. E2 levels were retrospectively analyzed to evaluate if patients had incomplete OFS and if clinical management changed based on those levels. The primary outcome was proportion of patients identified per the E2 monitoring protocol that fail to achieve OFS for two consecutive levels over an 18-month period. Nominal data were compared using the chi-squared or Fisher's exact test, and continuous data using the Mann Whitney U or student's t-test, where appropriate. A total of 85 patients were reviewed at the time of analysis. Fifty-three patients (62.4%) achieved complete OFS (three consecutive E2 levels within goal), compared to 17 patients (20%) demonstrating incomplete OFS. Seven patients (8.2%) did not have enough consecutive levels demonstrating complete or incomplete OFS and E2 lab monitoring continues. Eight patients (9.4%) declined lab monitoring. Out of the 17 patients with incomplete OFS, 14 underwent a change in their GnRH agonist as an intervention aimed at achieving complete OFS. Among these 14 patients, 7 successfully attained OFS, 5 continued to experience incomplete OFS, and 2 opted to decline future monitoring. . More patients were chemotherapy naïve in the continued incomplete OFS group compared to those who had complete OFS after intervention (p = 0.010). Our study has shown a trend toward the need for checking E2 levels to assess for incomplete OFS and that changing GnRH agonist agent can improve rates of complete OFS for some patients. Additionally, our study has shown that chemotherapy naïve patients experience more incomplete OFS; however, further data is needed to validate these results.