Fulvestrant is an estrogen receptor antagonist, mainly indicated for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

I. Indications

1. Monotherapy

Fulvestrant is indicated in postmenopausal women with breast cancer for the following:

(1) Hormone receptor (HR)-positive, HER2-negative advanced breast cancer with no prior endocrine therapy.

(2) HR-positive advanced breast cancer with disease progression after endocrine therapy.

2. Combination Therapy

Fulvestrant may be used in combination with the following agents:

(1) In combination with ribociclib: for postmenopausal women with HR‑positive, HER2‑negative advanced or metastatic breast cancer, as initial endocrine therapy or following disease progression on endocrine therapy.

(2) In combination with palbociclib or abemaciclib: for women with HR‑positive, HER2‑negative advanced or metastatic breast cancer with disease progression after endocrine therapy.

Note: Peri- or premenopausal women receiving combination therapy should also be treated with an LHRH agonist.

II. Contraindications

1. Absolute Contraindication

Fulvestrant is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

2. Recognition of Hypersensitivity Symptoms

Hypersensitivity reactions may present as:

Pruritus or urticaria, swelling of the face, lips, tongue or throat, and dyspnea.

III. Use in Special Populations

1. Patients with Hepatic Impairment

(1) Moderate hepatic impairment (Child‑Pugh Class B): the recommended dose is 250 mg administered as a single gluteal injection once monthly.

(2) Severe hepatic impairment (Child‑Pugh Class C): not evaluated; use is not recommended.

2. Patients at Risk of Bleeding

As fulvestrant is administered intramuscularly, caution is required in the following populations:

Patients with thrombocytopenia, patients with hemorrhagic disorders, and patients receiving anticoagulants (e.g., warfarin).

3. Pregnant Women

(1) Fulvestrant may cause fetal harm. Effective contraception should be used during treatment and for 1 year after the last dose.

(2) If pregnancy is suspected or confirmed, the physician should be informed immediately.

4. Lactating Women

(1) It is unknown whether fulvestrant is excreted in human milk.

(2) Breastfeeding is not recommended during treatment and for 1 year after the last dose.

5. Pediatric Population

(1) The safety and efficacy of fulvestrant in children have not been established.

(2) In a study in female pediatric patients aged 1–8 years, adverse reactions occurred in 27%, with no reports of death or treatment discontinuation.

6. Geriatric Population

(1) Objective response rates observed in patients aged 65 years and older were lower than in younger patients; however, no dose adjustment is necessary.

7. Patients with Renal Impairment

(1) No specific dose adjustment recommendations are currently available.

IV. Drug Interactions

1. No Known Clinically Relevant Interactions

Fulvestrant does not significantly inhibit major CYP enzymes (including CYP3A4). No clinically meaningful interactions have been observed with the following drugs:

CYP3A4 inhibitors (e.g., ketoconazole), CYP3A4 inducers (e.g., rifampicin), palbociclib, abemaciclib, ribociclib.

V. Precautions

1. Administration Site Precautions

(1) Care should be taken to avoid sciatic nerve injury when injecting into the gluteus maximus muscle.

(2) If numbness, tingling, or weakness in the leg occurs after injection, medical attention should be sought promptly.

2. Effects on Laboratory Tests

Due to structural similarity, fulvestrant may interfere with immunoassays for estradiol, leading to falsely elevated results, which should be considered when interpreting test results.