Anastrozole (Arimidex)
Anastrozole is the estrogen-blocking drug starting with "A" that serves as first-line adjuvant therapy for postmenopausal women with hormone receptor-positive early breast cancer. 1
Mechanism and Clinical Role
Anastrozole is a third-generation nonsteroidal aromatase inhibitor that blocks the aromatase enzyme, preventing conversion of androgens to estrogen in postmenopausal women. 2 This mechanism achieves near-maximal suppression of both serum and intratumoral estrogen levels to below detectable limits, with studies demonstrating 89% suppression of intratumoral estradiol and 83% suppression of estrone. 3
FDA-Approved Indications
The FDA has approved anastrozole for three specific settings in postmenopausal women: 1
- Adjuvant treatment of hormone receptor-positive early breast cancer
- First-line treatment of hormone receptor-positive or unknown locally advanced or metastatic breast cancer
- Second-line treatment of advanced breast cancer after tamoxifen failure
Guideline-Recommended Use
The 2006 St. Gallen guidelines marked a pivotal shift by naming anastrozole specifically as one of the best options for postmenopausal women with hormone-sensitive disease, recommending either 5 years of anastrozole alone or anastrozole following 2-3 years of tamoxifen to complete 5 years of adjuvant therapy. 4 This recommendation prioritizes starting with the most effective treatment available rather than defaulting to tamoxifen first, as the risks associated with tamoxifen cannot be offset by later aromatase inhibitor use. 4
Superiority Over Tamoxifen
Head-to-head trials demonstrate that anastrozole provides superior disease-free survival compared to tamoxifen in hormone receptor-positive tumors, with treatment benefits extending to 100 months following breast surgery. 5 The ATAC trial in 9,366 patients showed anastrozole was significantly superior for disease-free survival (p=0.013) and incidence of contralateral breast cancer (p=0.007). 6
Tolerability Profile Compared to Tamoxifen
Anastrozole demonstrates a more favorable safety profile than tamoxifen in several domains: 6
- Lower risk of endometrial cancer (p=0.02)
- Lower risk of vaginal bleeding/discharge (p<0.0001)
- Lower risk of thromboembolic events (p=0.0006)
- Lower risk of ischemic cerebrovascular events (p=0.0006)
- Lower risk of hot flushes (p<0.0001)
However, anastrozole carries higher risk of musculoskeletal disorders and bone fractures (p<0.0001 for both), though fracture risk is restricted to the treatment period. 5, 6
Alternative Aromatase Inhibitors
When anastrozole is not tolerated or appropriate, letrozole (2.5 mg daily) and exemestane (25 mg daily) serve as equivalent alternatives, with all three third-generation aromatase inhibitors demonstrating similar efficacy in clinical trials. 7 Letrozole may provide superior estrogen suppression in head-to-head studies, while exemestane offers a distinct steroidal mechanism with irreversible enzyme binding. 7
Critical Prescribing Caveat
Anastrozole is effective only in postmenopausal women. 7 In premenopausal patients, aromatase inhibitors must be combined with ovarian function suppression (LHRH agonists, surgical oophorectomy, or radiotherapeutic ablation) because peripheral aromatization is not the primary estrogen source in this population. 7