Fulvestrant (DB00947): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Evolving Role in the Treatment of HR-Positive Breast Cancer

Executive Summary

Fulvestrant represents a paradigm shift in the endocrine management of hormone receptor (HR)-positive breast cancer. As the first-in-class Selective Estrogen Receptor Degrader (SERD), its introduction provided a novel therapeutic strategy for a disease predominantly driven by estrogen signaling.[1] The core of Fulvestrant's clinical utility lies in its unique dual mechanism of action: it not only competitively antagonizes the estrogen receptor (ER) but also actively promotes its degradation. This complete abrogation of ER signaling, devoid of the partial agonist effects seen with Selective Estrogen Receptor Modulators (SERMs) like tamoxifen, established a new class of endocrine therapy.[2]

The clinical journey of Fulvestrant has been one of continuous evolution. Initially approved as a second-line monotherapy for postmenopausal women whose disease had progressed on prior anti-estrogen therapy, its role was significantly expanded based on pivotal clinical trial data.[7] The CONFIRM trial established the superiority of a 500 mg dosing regimen over the initial 250 mg dose, optimizing its therapeutic potential.[9] Subsequently, the FALCON trial demonstrated its superiority over the aromatase inhibitor anastrozole in the first-line setting, positioning Fulvestrant as a key monotherapy option for treatment-naïve patients.[11]