Hormonal suppression in premenopausal patients with estrogen receptor-positive breast cancer: a randomized trial comparing monthly versus trimonthly GnRH analogs

Abstract

Background: Currently the standard of care for premenopausal women with estrogen receptor-positive breast cancer is the combined use of a gonadotropin-releasing hormone (GnRH) analog with either tamoxifen or an aromatase inhibitor in patients at high risk for relapse or when it is deemed necessary to optimize ovarian function suppression. Monthly GnRH analogs have been used for years but, recently, longer-acting formulations have been gaining approval. Yet, there is still a gap of evidence regarding the use of longer-acting formulations; only a few studies exist that examine their efficacy in breast cancer and compare them to the monthly formulations. It is the investigators’ hypothesis that trimonthly injections, which are more convenient for the patient and ensure better compliance, are better suited for use in breast cancer patients and may induce equally effective estrogen suppression as the monthly injections. Aim: A comparison of trimonthly versus monthly GnRH analogs in eliciting ovarian function suppression in premenopausal patients with estrogen receptor-positive breast cancer. Methodology: This is a prospective randomized open-label trial involving 25 premenopausal patients that were randomized to receive either a monthly or a trimonthly GnRH analog. Estrogen (E2) levels, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured on day 0 and on week 12. Patients, also, completed a questionnaire regarding exhibiting amenorrhea and other side-effects of the analogs. Results: All patients (N=25; 100%) from both groups achieved ovarian function suppression according to the criteria set by the researchers, which are E2 levels <30 pg/mL and amenorrhea. Both groups exhibited a statistically significant decrease (almost by 50%) in E2 levels by week 12 (monthly group: E2 levels’ decrease equal to -18.5 pg/mL, p=0.00293; trimonthly group: E2 levels’ decrease equal to -13.9 pg/mL, p=0.0002441). On the contrary, FSH and LH levels did not show a statistically significant difference in either group. Moreover, when the two groups were compared, there was no statistically significant difference in the variation of all hormone levels between day 0 and week 12. All patients developed amenorrhea. There were no statistically significant differences in the number of side-effects between the two groups, even though the trimonthly group had fewer (in absolute number) side-effects than the monthly. Conclusion: This study demonstrates that the trimonthly formulations of GnRH analogs are equally effective in eliciting ovarian function suppression and present a similar percentage of side-effects as the monthly formulations, with the added benefit that patients need not undergo monthly injections.