Anastrozole in Breast Cancer Treatment
Primary Indications
Anastrozole is a selective aromatase inhibitor indicated for postmenopausal women with hormone receptor-positive breast cancer in three clinical settings: adjuvant treatment of early-stage disease, first-line treatment of locally advanced or metastatic disease, and second-line treatment after tamoxifen failure. 1
Adjuvant Treatment of Early-Stage Breast Cancer
Anastrozole 1 mg daily for 5 years is superior to tamoxifen for reducing breast cancer recurrence in postmenopausal women with hormone receptor-positive early breast cancer (HR for disease-free survival 0.85,95% CI 0.76-0.94, p=0.003), though no overall survival difference was observed at 100 months follow-up (HR 0.90,95% CI 0.75-1.07). 2
Sequential therapy with tamoxifen followed by anastrozole provides an overall survival benefit compared to tamoxifen alone (HR 0.53,95% CI 0.28-0.99, p=0.045). 2
Anastrozole should be used as initial adjuvant therapy or as sequential therapy after 2-3 years of tamoxifen, based on the more favorable toxicity profile compared to tamoxifen. 2
Critical caveat: Aromatase inhibitors are not active in women with functioning ovaries and should never be used in premenopausal women or those with unreliable assessment of ovarian function due to treatment-induced amenorrhea. 2
First-Line Treatment of Metastatic Breast Cancer
Third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) are recommended as first-line treatment for postmenopausal patients with hormone receptor-positive metastatic breast cancer based on more favorable toxicity profiles, though tamoxifen remains a valuable option. 2
Anastrozole is at least as effective as tamoxifen in metastatic disease, with some studies showing longer time to progression. 2
Endocrine therapy should be offered as first option to women with: long disease-free interval (>2 years), no or limited visceral involvement, limited metastatic sites, and slow disease progression. 2
Second-Line Treatment After Tamoxifen Failure
Anastrozole is indicated for advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. 1
Patients with ER-negative disease and those who did not respond to previous tamoxifen therapy rarely respond to anastrozole. 1
Third-generation aromatase inhibitors or fulvestrant are recommended for second-line treatment after tamoxifen failure based on favorable side-effect profiles. 2
Breast Cancer Risk Reduction
Anastrozole 1 mg daily for 5 years should be discussed as an option to reduce invasive breast cancer risk in postmenopausal women at increased risk (HR 0.47,95% CI 0.32-0.68, p<0.0001), with predicted 7-year cumulative incidence of 2.8% versus 5.6% with placebo. 2, 3
Women most likely to benefit have: atypical hyperplasia or lobular carcinoma in situ, 5-year BCRAT risk ≥3%, 10-year IBIS/Tyrer-Cuzick risk ≥5%, or relative risk ≥4× population risk (ages 40-44) or ≥2× (ages 45-69). 2
Anastrozole should never be prescribed for breast cancer risk reduction in premenopausal women. 2
Mechanism of Action
Anastrozole is a selective non-steroidal aromatase inhibitor that suppresses estrogen biosynthesis by specifically inhibiting the aromatase enzyme, which converts adrenal androgens to estrone and estradiol in postmenopausal women. 1
Anastrozole 1 mg daily reduces estradiol by approximately 70% within 24 hours and 80% after 14 days, with suppression maintained for up to 6 days after cessation. 1
It has no detectable effect on adrenal corticosteroid or aldosterone formation and does not possess direct progestogenic, androgenic, or estrogenic activity. 1
Adverse Effects and Management
Musculoskeletal Effects
Articular symptoms including joint stiffness, arthralgias, and arthritis are well-known side effects of anastrozole. 4
Anastrozole is more commonly associated with musculoskeletal symptoms, osteoporosis, and increased bone fracture rates compared to tamoxifen. 2
Before initiating anastrozole, assess baseline fracture risk and measure bone mineral density; history of osteoporosis or severe bone loss is a relative contraindication. 4
For patients with moderate bone mineral density loss, consider bone-protective agents such as bisphosphonates or RANKL inhibitors. 4
All patients should be encouraged to exercise regularly and take adequate calcium and vitamin D supplementation. 4
Cardiovascular Effects
Women with early breast cancer and history of ischemic heart disease taking anastrozole may experience increased symptoms of decreased blood flow to the heart compared to tamoxifen recipients. 1
Anastrozole is associated with hypertension. 4
Other Adverse Effects
Vasomotor symptoms (hot flashes, night sweats) and vaginal dryness occur with both anastrozole and tamoxifen. 2, 4
Anastrozole is associated with hypercholesterolemia and dry eyes. 4
Unlike tamoxifen, anastrozole has lower rates of endometrial cancer, gynecologic complaints, and thromboembolic events. 2
Critical Drug Interactions
Anastrozole should not be taken with tamoxifen, as concurrent use lowers anastrozole blood levels and reduces efficacy. 1
- Medicines containing estrogen (hormone replacement therapy, birth control pills, estrogen creams, vaginal rings, vaginal suppositories) may prevent anastrozole from working properly. 1