What are the common side effects of Anastrozole (aromatase inhibitor) in postmenopausal women with hormone receptor-positive breast cancer?

Anastrozole Side Effects in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer

Anastrozole causes several important side effects that directly impact quality of life, with musculoskeletal symptoms and bone loss being the most clinically significant concerns requiring proactive monitoring and management. 1, 2

Musculoskeletal Side Effects (Most Common Reason for Discontinuation)

• Joint-related symptoms including arthritis, arthralgias, and joint stiffness occur in 25-35.6% of patients and represent a leading cause of treatment discontinuation. 1, 2, 3
• Musculoskeletal pain results from profound estrogen suppression caused by anastrozole. 2
• Back pain occurs in approximately 10% of patients. 3
• Carpal tunnel syndrome occurs more frequently with anastrozole (2.5%) compared to tamoxifen (0.7%). 3

Bone Health Complications (Most Serious Quality-of-Life Threatening Effect)

• Anastrozole significantly increases bone loss and fracture risk, with fracture rates of 10% compared to 7% with tamoxifen. 1, 3, 4
• Mean decreases in both lumbar spine and total hip bone mineral density occur compared to baseline. 3
• Fractures specifically affect spine, hip, and wrist. 1, 3
• Severe osteoporosis (T-score <-4 or >2 vertebral fractures) is a relative contraindication to anastrozole use. 1

Mandatory Bone Protection Protocol

• Baseline bone mineral density measurement is required before starting treatment. 1
• All patients must receive calcium and vitamin D supplementation plus weight-bearing exercise. 1, 3
• Consider bisphosphonates or RANKL inhibitors in patients with moderate bone loss. 1
• Use anastrozole with caution in postmenopausal women with moderate bone mineral density loss. 1

Vasomotor Symptoms

• Hot flashes occur in 35.7% of patients, though this is actually lower than tamoxifen (40.9%). 5, 3
• Night sweats are common but occur less frequently than with tamoxifen. 2

Cardiovascular and Metabolic Effects

• Hypertension is a common adverse effect requiring monitoring. 3
• Elevated serum cholesterol occurs in 9% of patients versus 3.5% with tamoxifen. 3
• Stroke risk is increased compared to tamoxifen (2.0% vs 2.8%). 1, 2, 3
• In women with pre-existing ischemic heart disease, ischemic cardiovascular events occur in 17% versus 10% with tamoxifen. 3
• Angina pectoris occurs in 2.3% of patients overall, but 11.6% in those with pre-existing ischemic heart disease. 3

Genitourinary and Gynecologic Effects

• Vaginal dryness and dyspareunia (painful intercourse) occur more frequently with anastrozole than tamoxifen. 1, 2
• Vaginal bleeding occurs significantly less with anastrozole (5%) compared to tamoxifen (10%). 3, 4
• Vaginal discharge is markedly reduced with anastrozole (3.5%) versus tamoxifen (13.2%). 5, 3
• Endometrial cancer risk is significantly lower with anastrozole (0.2%) compared to tamoxifen (0.8%). 5, 6, 3, 4

Thromboembolic Events (Significantly Reduced Compared to Tamoxifen)

• Venous thromboembolic events occur in 2.8% with anastrozole versus 4.5% with tamoxifen. 5, 6, 3, 4
• Cerebrovascular events occur in 2.0% with anastrozole versus 2.8% with tamoxifen. 5, 6, 3, 4

Other Common Side Effects

• Asthenia (weakness) occurs in >10% of patients. 3
• Nausea and vomiting occur in >10% of patients. 3, 7, 8
• Headache occurs in up to 18% of patients. 3, 7
• Depression is reported in >10% of patients. 3
• Peripheral edema (leg/ankle swelling) occurs in up to 9% of patients. 3, 7
• Dry eyes are a common complaint. 1, 2
• Rash occurs in >10% of patients. 3
• Increased cough, dyspnea, and pharyngitis each occur in >10% of patients. 3
• Insomnia occurs in >10% of patients. 3
• Lymphedema occurs in >10% of patients. 3

Rare but Serious Adverse Reactions

• Allergic reactions including angioedema and anaphylaxis can occur. 3
• Hepatic changes including liver inflammation with jaundice, liver pain, or liver swelling may develop. 3
• Skin reactions including Stevens-Johnson syndrome and erythema multiforme have been reported. 3

Critical Clinical Caveats

• Treatment discontinuation due to adverse effects occurs in 11.1% of patients, which is lower than tamoxifen (14.3%). 5
• Hot flashes are the most common reason for discontinuation in both treatment groups, though fewer patients discontinue anastrozole than tamoxifen for this reason. 3
• Joint symptoms may improve with continued use or may require switching to alternative endocrine therapy. 2
• Anastrozole only works in truly postmenopausal women and must never be used in premenopausal women. 1, 6, 2

Comparative Tolerability Profile

Overall, anastrozole demonstrates superior tolerability compared to tamoxifen regarding life-threatening complications (endometrial cancer, thromboembolic events, cerebrovascular events), but causes more musculoskeletal symptoms and bone loss. 5, 3, 4 The side-effect profiles are distinctly different between the two drugs, allowing for individualized selection based on patient-specific risk factors. 1