Fulvestrant

Fulvestrant is a selective estrogen receptor degrader (SERD) used in the treatment of hormone receptor–positive breast cancer. It binds to the estrogen receptor (ER) with high affinity and promotes degradation of the receptor, thereby reducing estrogen signaling in tumor cells.

Fulvestrant is approved for postmenopausal women with estrogen receptor–positive, HER2-negative (ER+/HER2−) advanced or metastatic breast cancer. It is used after disease progression on or after antiestrogen therapy, such as an aromatase inhibitor. It can be given as monotherapy or in combination with CDK4/6 inhibitors to improve progression-free survival in selected patients.

The drug is administered by intramuscular injection, typically into the buttock. The standard dosing regimen consists of loading doses of 500 mg on days 1, 15, and 29, followed by 500 mg every 28 days. Dosing may vary based on regional labeling or combinations with other agents.

Mechanistically, fulvestrant acts as a pure antiestrogen by causing degradation of ERα, resulting in a reduction of estrogen-driven transcription. Its mechanism differs from receptor blockade alone, providing a decrease in receptor availability.

Common adverse events include hot flashes, fatigue, injection-site reactions, nausea, headache, and musculoskeletal pain. Less frequently, liver enzyme elevations or hypersensitivity reactions can occur; monitoring liver function and treatment tolerance is recommended.