Fulvestrant, an estrogen receptor antagonist, is clinically used to treat hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women, either as monotherapy or combined with CDK4/6 inhibitors, demonstrating efficacy in delaying disease progression and improving progression-free survival.

Mechanism and Clinical Efficacy of Fulvestrant in HR-Positive Advanced Breast Cancer

Fulvestrant exerts therapeutic effects by competitively binding to estrogen receptors (ER), inducing ER downregulation, and inhibiting estrogen-dependent tumor growth. As monotherapy, it significantly prolongs progression-free survival (PFS) versus lower-dose regimens (CONFIRM trial: median PFS 6.5 vs. 5.4 months; HR 0.80) and outperforms anastrozole in treatment-naïve patients (FALCON trial: median PFS 16.6 vs. 13.8 months; HR 0.797). In combination with CDK4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), fulvestrant synergistically enhances efficacy, doubling median PFS compared to placebo combinations (PALOMA-3: 9.5 vs. 4.6 months; HR 0.461). It is particularly effective in patients without prior endocrine therapy or with disease progression post-endocrine treatment. Hepatic impairment necessitates dose reduction (250 mg for moderate impairment), but renal impairment does not alter pharmacokinetics. Clinical benefits include objective tumor response (13.8–48.1% in trials) and stable disease maintenance, though long-term survival data remain under investigation. Adverse effects, such as injection site reactions or hepatic enzyme elevations, are manageable and do not negate therapeutic advantages.