Dr Graff on the Efficacy and Safety of GnRH Agonists for Premenopausal Women With Breast Cancer

“When we combine OFS and fertility preservation, patients can later benefit from taking a break from these therapies, successfully moving toward pregnancy, and then go back on those therapies after a 2-year break to have their optimal family and breast cancer outcomes.”

Stephanie L. Graff, MD, FACP, FASCO, director, breast oncology, Lifespan Cancer Institute; associate professor, medicine, Warren Alpert Medical School; co-leader, Breast Cancer Translational Research Disease Group, Brown University’s Legorreta Cancer Center, discusses prior data supporting the use of gonadotropin-releasing hormone (GnRH) agonists to preserve fertility for premenopausal women with breast cancer undergoing chemotherapy.

Final results from the phase 3 POEMS trial (NCT00068601), published in 2018 in the Journal of the National Cancer Institute, demonstrated that administering the GnRH agonist goserelin during chemotherapy significantly reduced the risk of ovarian failure in patients with premenopausal, hormone receptor (HR)–negative breast cancer, Graff reports. This intervention was associated with a high rate of ovarian function restoration post-treatment, improving the likelihood of future pregnancies, she states. Importantly, the use of GnRH agonists improved disease-free survival (DFS) and overall survival outcomes in the HR-negative patient population.

Ovarian function suppression (OFS) has also proven to be beneficial in HR-positive breast cancer, Graff continues. An Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis, findings from which were presented at the 2023 ASCO Annual Meeting, highlighted that OFS combined with endocrine therapy significantly improves outcomes, particularly for patients with high-risk disease, she details.

Additionally, the POSITIVE study (NCT02308085) provided reassurance for women with HR-positive breast cancer desiring pregnancy, Graff reports. The trial demonstrated that a temporary interruption of endocrine therapy to attempt conception did not compromise DFS, she states. Patients were able to pause therapy for up to 2 years, pursue pregnancy, and resume treatment thereafter, Graff notes. This allows patients to balance optimal family-building goals with favorable breast cancer outcomes, Graff says. Together, these data support a comprehensive approach to fertility preservation and OFS, allowing women with breast cancer to maintain reproductive potential and achieve optimal cancer outcomes, Graff concludes.