Incomplete Estrogen Suppression With Gonadotropin-Releasing Hormone Agonists May Reduce Clinical Efficacy in Premenopausal Women With Early Breast Cancer.

Abstract

Background Oophorectomy was the first endocrine therapy for breast cancer but has been largely superseded by gonadotropin-releasing hormone agonists (GnRHas) as a result of their reversible, less invasive suppression of ovarian function. The concept was developed more than two decades ago that GnRHa efficacy in treating estrogen receptor–positive breast cancer in premenopausal women might be improved by combination with an antiestrogen or aromatase inhibitor (AI) to antagonize or inhibit the synthesis of the residual nongonadal estrogen. Now, the results of three phase III studies comparing ovarian function suppression (OFS) with and without tamoxifen or comparing OFS plus tamoxifen with OFS plus AI are available; however, the results are conflicting. Here we consider the endocrine pharmacology of these combination therapies and provide potential explanations for the variable clinical findings as well as a possible means of improving combination therapy involving OFS.