Measuring Ovarian Escape in Premenopausal Estrogen Receptor-Positive Breast Cancer Patients on Ovarian Suppression Therapy

Abstract

Purpose. To evaluate the proportion of premenopausal women who experience persistent ovarian escape (OE) while receiving ovarian suppression (OS) therapy for estrogen receptor positive (ER+) breast cancer treatment. The study also examines clinical factors that may predispose to higher risk of persistent OE. Methods/Materials. This was a retrospective, "real-world" study to evaluate premenopausal women receiving adjuvant endocrine OS therapy. The primary objective was to measure the percentage of persistent OE within the first 3 months of OS injections (using either leuprolide or goserelin). The secondary objective was to associate baseline clinical data (age, body mass index (BMI), and previous chemotherapy) with the probability of OE. Results. Of the 46 patients included in this analysis, 11 (23.9%) women did not achieve OS within 3months. Three women (6.5%) remained in OE at 12 months. Older age (Odds Ratio 0.86 (0.76-0.98), p=0.024) was associated with lower chance of developing OE. BMI, previous chemotherapy, and drug used (tamoxifen versus aromatase inhibitor) did not correlate with the likelihood of OE in this patient cohort. Conclusion. Among the premenopausal women who did not attain complete ovarian suppression, young age was a significant risk factor for likelihood of OE. Although the clinical relevance of this finding is not yet known, it should prompt further studies to determine whether inadequate OS is associated with higher recurrence risk for ER+ breast cancer patients. The Oncologist 2021;9999:• • Implications for Practice: Because up to a quarter of premenopausal women do not attain adequate ovarian suppression within the first three months of GnRH agonist therapy, bloodwork should be checked to ascertain hormone levels prior to starting aromatase inhibitor therapy, and at regular intervals, for these women.

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer

“…This patient was 35 years old at the time of diagnosis and had a BMI between 22.7 and 23.4 kg/m 2 during the follow-up period. In several studies on OFS, ovarian escape cases were observed during OFS administration (28,30); however, to our knowledge, to date, no considerable results have shown the prognostic significance of ovarian escape, and currently, there is no guideline for such cases. Accordingly, careful follow-up and further investigations are needed for ovarian escape cases.…”

A method to detect fulvestrant interference in estradiol in breast cancer patients

“…Since efficacy data in premenopausal women became available ( 4 , 5 ), fulvestrant (with GnRH for ovarian suppression) in combination with CDK4/6 or in monotherapy is a widely used option in ABC premenopausal women ER+. Failure to attain complete ovarian suppression with GnRH can however occur ( 7 , 8 ) and may conceivably be associated with higher recurrence risk ( 9 , 10 ). So, although not a level I recommendation, routine monitorization of estradiol in these patients may be considered.…”

“…The reference interval for considering post-menopausal females cutoff is <32.2 pg/mL ( 16 ). The definition for complete ovarian suppression while on a GnRH agonist is not clearly defined ( 8 ). We used the estradiol cut-off levels for naturally postmenopausal women.…”

“…In premenopausal patients, fulvestrant requires the combination with a gonadotropin‐releasing hormone (GnRH) agonist therapy for ovarian suppression (OS) ( 6 ). However, studies show that 17–24% ( 7 , 8 ) of premenopausal women do not experience complete OS with GnRH agonists therapy and, although still not clear, this may contribute to poorer outcomes ( 7 , 9 , 10 ). Some authors ( 7 , 8 ) suggest that estradiol measurement should routinely be carried out in these patients to ensure that they are indeed fully castrated.…”

Revisiting Adjuvant Hormone Therapy in Premenopausal Women With Breast Cancer: Escalation and De-Escalation

“…Young age was associated with a higher chance of developing ovarian escape. 15 Chlebowski et al 16 conducted a meta-analysis and concluded that given the discordance between DFS and OS and inconsistent estrogen suppression with OFS plus aromatase inhibitor, it is premature to be recommended as a routine approach for premenopausal woman. As a result, in premenopausal women on OFS, estrogen levels should still be checked if aromatase inhibitors are used rather than tamoxifen.…”