What is Anastrozole used for?

What is Anastrozole Used For?

Anastrozole is an aromatase inhibitor used primarily for treating hormone receptor-positive breast cancer in postmenopausal women and for reducing breast cancer risk in high-risk postmenopausal women. 1

FDA-Approved Treatment Indications

Anastrozole has three FDA-approved uses in postmenopausal women with breast cancer 1:

• Adjuvant treatment of hormone receptor-positive early breast cancer following surgery 1
• First-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer 1
• Second-line treatment of advanced breast cancer after disease progression on tamoxifen therapy 1

Anastrozole does not work in premenopausal women because it cannot adequately suppress ovarian estrogen synthesis 2, 1

Breast Cancer Risk Reduction (Off-Label)

While not FDA-approved for prevention, anastrozole 1 mg/day for 5 years is recommended by ASCO as an option to reduce breast cancer risk in postmenopausal women at increased risk 2:

Who Should Consider Anastrozole for Risk Reduction:

Postmenopausal women with one or more of the following 2:

• Atypical ductal or lobular hyperplasia or lobular carcinoma in situ (LCIS)
• 5-year risk ≥3% by the National Cancer Institute Breast Cancer Risk Assessment Tool
• 10-year risk ≥5% by the IBIS/Tyrer-Cuzick Risk Calculator
• Relative risk ≥4 times the population risk (ages 40-44) or ≥2 times (ages 45-69)

Evidence for Risk Reduction:

The IBIS-II trial demonstrated that anastrozole reduced breast cancer incidence by approximately 50% compared to placebo in high-risk postmenopausal women 2. The reduction was specifically for estrogen receptor-positive cancers (HR 0.42,95% CI 0.25-0.71) 2.

Treatment of Ductal Carcinoma In Situ (DCIS)

For postmenopausal women with ER-positive DCIS treated with breast-conserving therapy, anastrozole is an alternative to tamoxifen 2:

• The IBIS-II trial showed anastrozole was non-inferior to tamoxifen for preventing recurrence in DCIS (HR 0.89,95% CI 0.64-1.23) 2
• The NSABP B-35 study demonstrated anastrozole significantly improved breast cancer-free interval compared to tamoxifen (HR 0.73,95% CI 0.56-0.96) 2
• Anastrozole may be particularly beneficial for women under age 60 or those with concerns about thromboembolic events 2

Mechanism of Action

Anastrozole works by blocking the aromatase enzyme, which is responsible for converting androgens to estrogens in peripheral tissues 3, 4. In postmenopausal women, peripheral tissues are the main source of estrogen since ovarian production has ceased 2.

Anastrozole suppresses plasma estrogen levels by 84-94% and intratumoral estrogen levels by approximately 89% for estradiol, 83% for estrone, and 73% for estrone sulfate 5.

Dosing

The standard dose is 1 mg orally once daily 2, 1:

• For adjuvant treatment: 5 years duration 6
• For risk reduction: 5 years duration 2
• Can be taken with or without food 1

Important Contraindications and Warnings

Anastrozole should NEVER be used in 2, 7, 1:

• Premenopausal women (ineffective and potentially harmful)
• Pregnant women or women who may become pregnant (may harm fetus)
• Women currently breastfeeding

Do not combine anastrozole with 1:

• Tamoxifen (reduces anastrozole effectiveness)
• Estrogen-containing medications (hormone replacement therapy, birth control pills, estrogen creams)

Key Side Effects to Monitor

Bone health concerns 6, 1:

• Increased risk of bone fractures, particularly spine, hip, and wrist
• Bone mineral density should be measured before starting and during treatment
• Consider bisphosphonates or RANKL inhibitors for patients at risk
• Ensure adequate calcium and vitamin D supplementation

Common side effects 2, 1:

• Joint stiffness and arthralgias (more common than with tamoxifen)
• Vasomotor symptoms (hot flashes, night sweats)
• Hypertension
• Dry eyes
• Vaginal dryness

Cardiovascular considerations 1:

• Women with history of ischemic heart disease may experience worsening symptoms
• Seek immediate medical attention for new or worsening chest pain or shortness of breath

Comparative Efficacy

In adjuvant treatment of early breast cancer, anastrozole demonstrated superior disease-free survival compared to tamoxifen in the ATAC trial (HR 0.83,95% CI 0.73-0.94) 2. The benefits extended to 100 months following surgery 8.

Anastrozole has fewer thromboembolic events (2.8% vs 4.5%), cerebrovascular events (2.0% vs 2.8%), and endometrial cancers (0.2% vs 0.8%) compared to tamoxifen 2.