What is Arimidex (anastrozole) and what is it used for?

What is Arimidex and What is it Used For?

Arimidex (anastrozole) is a non-steroidal aromatase inhibitor that blocks estrogen production in postmenopausal women and is FDA-approved for treating hormone receptor-positive breast cancer. 1

Mechanism of Action

Anastrozole works by specifically inhibiting the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. 1 In postmenopausal women, this enzyme-mediated conversion in peripheral tissues represents the sole source of estrogen. 1 By blocking this pathway, anastrozole reduces serum estradiol concentrations by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing, with suppression maintained for up to 6 days after stopping the medication. 1

Critically, anastrozole does not work in premenopausal women because aromatization of adrenal androgens is not a significant source of estradiol in this population—ovarian production dominates. 1

FDA-Approved Indications

Anastrozole is FDA-approved for three specific uses in postmenopausal women: 2

• Adjuvant treatment of hormone receptor-positive early breast cancer
• First-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer
• Treatment of advanced breast cancer in women with disease progression after tamoxifen therapy

Clinical Evidence for Adjuvant Use

The landmark ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial established anastrozole's superiority over tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer. 2 At 68 months median follow-up, anastrozole demonstrated:

• Disease-free survival hazard ratio of 0.83 (95% CI, 0.73–0.94; P = .005) 2
• Time to recurrence hazard ratio of 0.74 (95% CI, 0.64–0.87; P = .0002) 2
• Reduced contralateral breast cancers (OR 0.56; 95% CI, 0.32–0.98; P = .04) in hormone receptor-positive patients 2

Notably, no overall survival difference was demonstrated in ATAC (HR 0.97; 95% CI, 0.85–1.12; P = 0.7), though this remains a common finding across aromatase inhibitor trials. 2

Breast Cancer Risk Reduction (Off-Label)

Anastrozole 1 mg/day for 5 years is now recommended by ASCO as an alternative to tamoxifen, raloxifene, or exemestane for breast cancer risk reduction in postmenopausal women at increased risk. 2 This recommendation stems from the IBIS-II trial, which demonstrated significant reduction in estrogen receptor-positive breast cancers in high-risk postmenopausal women. 2

Women most likely to benefit include those with: 2

• Atypical ductal or lobular hyperplasia or lobular carcinoma in situ
• 5-year risk ≥3% by NCI BCRAT
• 10-year risk ≥5% by IBIS/Tyrer-Cuzick calculator
• Relative risk ≥4 times population risk (ages 40-44) or ≥2 times (ages 45-69)

However, anastrozole is NOT FDA-approved for breast cancer prevention—this remains an off-label use. 2

Dosing and Administration

The standard dose is 1 mg orally once daily. 3, 1 The optimal duration for adjuvant treatment is 5 years. 3 Anastrozole can be taken with or without food, though food reduces the rate (not extent) of absorption. 1

Critical Safety Considerations

Bone Health

Anastrozole causes bone thinning and increased fracture risk due to estrogen suppression. 1 The ATAC trial showed bone fractures occurred in 11.0% of anastrozole patients versus 7.7% on tamoxifen (P < .0001). 2

Before initiating treatment: 3

• Evaluate baseline fracture risk
• Measure bone mineral density
• Consider bone-protective agents (bisphosphonates, RANKL inhibitors) for at-risk patients
• Ensure adequate calcium and vitamin D supplementation with regular exercise

Cardiovascular Concerns

Women with pre-existing ischemic heart disease may experience increased symptoms of decreased cardiac blood flow compared to tamoxifen. 1 New or worsening chest pain or shortness of breath requires immediate medical evaluation. 1

Common Adverse Effects

Compared to tamoxifen, anastrozole causes: 2

• More frequent: Bone fractures (11.0% vs 7.7%), arthralgias (35.6% vs 29.4%)
• Less frequent: Endometrial cancer (0.2% vs 0.8%), venous thromboembolism (2.8% vs 4.5%), hot flushes (35.7% vs 40.9%), vaginal bleeding (5.4% vs 10.2%)

Absolute Contraindications

Do not prescribe anastrozole to: 4, 1

• Premenopausal women (ineffective due to ovarian estrogen production)
• Pregnant women or women able to become pregnant (may harm fetus)
• Women with severe allergic reactions to anastrozole

Drug Interactions

Never combine anastrozole with: 1

• Tamoxifen (reduces anastrozole blood levels and efficacy)
• Estrogen-containing medications (hormone replacement therapy, birth control pills, estrogen creams, vaginal rings, vaginal suppositories—all may interfere with efficacy)

Monitoring Requirements

Prior to and during treatment: 3

• Bone mineral density assessments
• Fracture risk evaluation
• Lipid profile monitoring (anastrozole does not affect adrenal corticosteroid or aldosterone synthesis, but monitor cholesterol) 1
• Prompt evaluation of abnormal vaginal bleeding