Ovarian Function Suppression With Luteinizing Hormone-Releasing Hormone Agonists for the Treatment of Hormone Receptor-Positive Early Breast Cancer in Premenopausal Women

Abstract

Chemotherapy and endocrine therapies are mainstays of treatment for early and advanced hormone receptor-positive (HR+) breast cancer. In premenopausal women with HR+ tumors, the benefits of adding ovarian function suppression (OFS) to endocrine therapy have been debated. Consequently, for many years, tamoxifen monotherapy has been the standard of care for endocrine treatment in the adjuvant setting. Recent studies have, however, provided new evidence that, in some premenopausal patients, OFS in combination with tamoxifen or aromatase inhibitors (AIs) can significantly increase survival versus tamoxifen alone. Luteinizing hormone-releasing hormone agonists (LHRHa), including goserelin, triptorelin, and leuprorelin, achieve OFS through sustained suppression of the release of follicle-stimulating hormone and luteinizing hormone from the pituitary. In turn, this suppresses production and secretion of estradiol, an ovarian hormone that supports cancer cell growth, survival, and proliferation. In this review, we discuss the clinical evidence supporting the addition of LHRHa to adjuvant endocrine therapies, including tamoxifen and AIs, for premenopausal women with breast cancer. We also discuss the role of LHRHa use in combination with adjuvant chemotherapy to preserve ovarian function and fertility in young patients with breast cancer. Finally, we discuss important practical aspects of the use of LHRHa in breast cancer treatment, including side-effects, patient adherence to treatment, and the use of slow-release, long-acting drug formulations.

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©

“…This adds further complexity to interpretating the results and drawing of conclusions with respect to menopause status as a predictor of RS. Therefore, the authors recommend judicious use of menopause status as a parameter to determine chemotherapy benefit in the setting of early-stage ER+/HER2− disease, and advocate for endocrine and ovarian suppression therapy prescription as a useful alternative in these patients [ 61 ].…”

Comparison of a histone deacetylase inhibitor plus exemestane with exemestane alone in hormone receptor‑positive advanced breast cancer that progressed on prior endocrine therapy: A meta‑analysis

“…For the perimenopausal and premenopausal patients included, although LHRHa was given simultaneously with the endocrine agents, the possibility that the administered LHRHa had impact on the final estimation could not be ruled out. After all, LHRHa, which was able to achieve OFS by sustained suppression of the release of follicle-stimulating hormone and luteinizing hormone from the pituitary ( 34 ), was reported as an effective endocrine approach in breast cancer ( 35 , 36 ). Second, the surgery, radiotherapy, line of therapy in the advanced setting, metastatic sites, tumor burden, prior chemotherapy regimens, as well as anti-estrogen treatment drugs and sequence in these eligible studies were also heterogeneous.…”

Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer—A Literature Review

“…The first consists of a bilateral oophorectomy or directed radiation to the ovaries [ 48 , 49 ]. The second is through a transient drug effect induced by OFS such as the luteinizing hormone (LH)-releasing hormone (LHRH) analogs [ 50 ]. As an initial effect of chemical castration, the serum estradiol and progesterone levels are increased.…”

“…As an initial effect of chemical castration, the serum estradiol and progesterone levels are increased. Its regular administration promotes downstream inhibitory cascades in the hypothalamic–pituitary axis to the gonadotropic hormones, decreasing the secretion of the follicle stimulating hormone (FSH) and LH, hence suppressing the gonadal estrogen levels [ 21 , 22 , 50 , 51 ].…”