What are the approximate incidence percentages of common adverse effects of tamoxifen 20 mg daily for 5 years in women with early‑stage hormone‑receptor‑positive breast cancer?

Tamoxifen Side Effect Profile: Incidence Percentages

The most common adverse effect of tamoxifen 20 mg daily is hot flashes, occurring in approximately 64% of women, while the most serious risks include endometrial cancer (3.1% with extended therapy vs 1.6% in controls) and venous thromboembolism (deep vein thrombosis 0.8%, pulmonary embolism 0.5% during standard 5-year therapy). 1, 2

Common Side Effects (>10% incidence)

Hot flashes and vasomotor symptoms:

• Hot flashes occur in 64% of tamoxifen-treated women versus 48% on placebo in adjuvant therapy trials 1, 2
• In premenopausal women with metastatic disease, hot flashes affect 33% on tamoxifen versus 46% with ovarian ablation 2

Gynecologic symptoms:

• Vaginal discharge occurs in 30% versus 15% on placebo 1, 2
• Irregular menses in 25% versus 19% on placebo 1, 2
• Amenorrhea in 16% of premenopausal women 2
• Vaginal dryness is commonly reported 1, 2

General symptoms:

• Fluid retention/edema: 32% versus 30% on placebo 1
• Nausea: 26% versus 24% on placebo 1

Serious Adverse Effects

Endometrial cancer:

• 3.1% incidence with 10 years of tamoxifen versus 1.6% in controls (event rate ratio 1.87,95% CI 1.30-2.34) 1
• In the aTTom trial: 1.3% (45 cases) in extended tamoxifen group versus 0.6% (20 deaths) in controls 1
• Annual hazard rate of 1.6 per 1,000 patient-years in randomized tamoxifen-treated patients 3
• Relative risk of 7.5 compared to placebo in NSABP B-14 trial 3

Venous thromboembolism (VTE):

• Deep vein thrombosis: 0.8% versus 0.2% on placebo during 5-year therapy 1, 2
• Pulmonary embolism: 0.5% versus 0.2% on placebo 1, 2
• Combined VTE/PE event rate ratio: 2.26 (95% CI 1.36-3.87) during active treatment, dropping to 1.14 (95% CI 0.52-2.53) after treatment cessation 4
• Overall thrombotic events through 5 years: 1.7% versus 0.4% on placebo 1

Stroke:

• Event rate ratio for stroke during years 5-9: 1.06 (95% CI 0.83-1.36) 1
• During years 10-14: rate ratio 1.25 1

Ischemic heart disease:

• Event rate ratio: 0.76 (95% CI 0.60-0.96), suggesting potential cardioprotective effect 1
• During years 5-9: rate ratio 0.62 (95% CI 0.46-0.85) 1

Moderate Frequency Side Effects (2-10%)

• Weight loss (>5%): 23% versus 18% on placebo 1
• Skin changes: 19% versus 15% on placebo 1
• Bone pain: 6% in tamoxifen group 2
• Musculoskeletal pain: 3% versus 0% with ovarian ablation 2
• Depression: 2% versus 2% with ovarian ablation 2
• Ovarian cysts: 3% versus 2% with ovarian ablation 2

Laboratory Abnormalities

• Increased SGOT: 5% versus 3% on placebo 1
• Increased bilirubin: 2% versus 1% on placebo 1
• Increased creatinine: 2% versus 1% on placebo 1
• Thrombocytopenia: 2% versus 1% on placebo 1
• Hypertriglyceridemia: relative risk 4.33 (95% CI 1.96-9.53) 5

Male-Specific Side Effects

In males with breast cancer, tamoxifen causes:

• Loss of libido (frequency not specified but leads to discontinuation) 2
• Impotence (frequency not specified but leads to discontinuation) 2
• Elevated LH, FSH, testosterone, and estrogen levels in oligospermic males 2

Critical Safety Monitoring Points

Absolute contraindications based on side effect risk:

• History of deep vein thrombosis or pulmonary embolism 1
• History of stroke or transient ischemic attack 1
• These contraindications exist because baseline VTE risk is already elevated, and tamoxifen increases it further 1, 2

Required monitoring:

• Baseline gynecologic examination before treatment initiation 1
• Annual gynecologic examinations 1
• Prompt evaluation of any abnormal vaginal bleeding (endometrial cancer surveillance) 1, 6

Duration-Dependent Risk Patterns

Extended therapy (10 years vs 5 years) increases:

• Endometrial cancer risk substantially (3.1% vs 1.6%) 1
• Pulmonary embolism risk (event rate ratio 1.87) 1

Post-treatment period:

• Most side effects diminish after stopping tamoxifen 4
• VTE risk returns to baseline after treatment cessation (RR 1.14, not statistically significant) 4
• Breast cancer risk reduction benefit persists for at least 10 years after stopping 4

Comparative Context with Aromatase Inhibitors

When comparing tamoxifen to aromatase inhibitors in postmenopausal women:

• Tamoxifen causes more gynecologic symptoms (20% vs 11%), more VTE (2% vs 1%), and more endometrial abnormalities (4% vs <1%) 7
• Tamoxifen causes fewer musculoskeletal symptoms (44% vs 50%), less hypertension (5% vs 6%), and less hyperlipidemia (3% vs 5%) 7
• Tamoxifen preserves bone density while aromatase inhibitors increase fracture risk 1, 6